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眼組織におけるプロスタノイドFP受容体の機能解析と緑内障治療薬への応用

木村(山岸), 麗子 東京大学 DOI:10.15083/0002006110

2023.03.20

概要

【別紙2】
審査の結果の要旨
氏名

木村(山岸) 麗子

本研究は、現在、緑内障治療における眼圧下降のターゲットであるプロスタノイドFP受容
体の眼圧制御に関わるメカニズムを明らかにするため、主作用である眼圧下降作用に加え
て副作用や付加的作用、さらにプロスタノイド受容体の将来への展開について検討した。
まず眼圧に及ぼす作用に対し、通常眼圧や一過性眼圧上昇に対するFP受容体の関与の有無
について野生型マウスおよび遺伝子改変マウスの眼圧についてマイクロニードル法を用い
て測定した。副作用については、アジア人に多く認められる上眼瞼深溝化 (DUES) に対す
るFP受容体の関与について培養脂肪細胞を用いた系で、既存のプロスタグランジン関連薬
(PG製剤)の分化脂肪細胞より産生される脂肪滴に対する作用について解析を行った。そ
して付加的作用については、ラット網膜神経節細胞(RGC)を用いた初代培養系で、既存のPG
製剤のRGC保護作用について検討を行った。最後に、新規開発中であるプロスタノイド
FP/EP3受容体デュアルアゴニストであるsepetaprostのマウス眼圧および房水流出に対す
る作用について解析を行い、下記の結果を得ている。
1.通常状態で各種プロスタノイド受容体を欠損させたマウスの眼圧と野生型マウス(WTマ
ウス)の眼圧を比較した場合、いずれの遺伝子欠損マウスにおいてもWTマウスに比べて
差が認められなかった。また、WTマウスへPGE2あるいはPGF2α点眼することで一過性眼圧
上昇が誘発されることが確認され、このPGE2/PGF2α誘発一過性眼圧上昇に対して、FP受
容体を欠損させたマウス(FPKOマウス)では、WTマウスに比べ一過性眼圧上昇の程度が
顕著であることが明らかになった。
2.PG製剤の副作用である上眼瞼深溝化 (DUES) に対するFP受容体の関与について検討し
た結果、3T3-L1細胞を用いた検討では、前駆脂肪細胞である3T3-L1細胞へ脂肪分化誘導
刺激を行った場合、脂肪分化誘導刺激で得られた分化脂肪細胞は明らかな脂肪滴産生を
認めた。これに対し、bimatoprostおよびlatanoprostなどで、分化脂肪細胞からの脂肪
滴産生は抑制されることが明らかとなった。また、WTマウスの腹部から得た初代前駆脂
肪細胞へ、分化誘導刺激を行うことで得たWTマウス分化脂肪細胞において、PG製剤処置
により、脂肪滴産生抑制が認められたのに対し、FPKOマウスから得た分化脂肪細胞では、
脂肪分化誘導刺激により脂肪滴産生は認められたものの、WTマウスで得られたPG製剤処
置による脂肪滴産生抑制作用は認められなかった。
3.付加的作用である眼圧非依存的な視神経保護作用について、RGCを用いて検討した結果、
既存のPG製剤によりapoptosis抑制を介したRGC細胞死抑制作用が認められた。
4.FP/EP3受容体デュアルアゴニストであるsepetaprostのマウス眼圧および房水流出に対
する作用について検討した結果、sepeteprostは既存のPG製剤に比べて顕著な眼圧下降
持続時間の延長を示すことが明らかとなった。また、この眼圧下降持続時間の延長作用
について、FPおよびEP3受容体欠損マウスを用いて検討した結果、FP受容体のみならず
EP3受容体への刺激が眼圧下降持続時間の延長に関与することが示された。さらに、
sepetaprostはFPおよびEP3受容体遺伝子欠損マウスを用いた検討から、FPおよびEP3受
容体刺激を介した房水流出量亢進作用を有することが示された。
以上、本論文は遺伝子改変マウスを用いた検討より、FP 受容体は一過性眼圧上昇に対して
眼圧を下降させる作用を有することが明らかとなり、これまで不明であった眼内での FP 受
容体の存在意義の一部を解明するに至った。また、分化脂肪細胞による脂肪滴産生や RGC
保護作用に FP 受容体が関与することを示した。さらに、新規に開発された sepetaprost の

マウス眼圧および房水動態に対する作用について、FP 受容体のみならず EP3 受容体も関
与することを初めて示したこととなった。これらのことは、すでに臨床で汎用されている
PG 製剤の作用機序解明、さらには FP 受容体の眼圧調節機構の解明に重要な貢献をなすと
考えられ、学位の授与に値するものと判断された。
よって博士(医学)の学位請求論文として合格と認められる。

この論文で使われている画像

参考文献

1.

The Japan Glaucoma Society Guidelines for Glaucoma (4th Edition).

Nippon Ganka Gakkai Zasshi 2018;122:3-51.

2.

Suzuki Y, Yamamoto T, Araie M, et al. [Tajimi Study review]. Nippon

Ganka Gakkai Zasshi 2008;112:1039-1058.

3.

Iwase A, Suzuki Y, Araie M, et al. The prevalence of primary

open-angle glaucoma in Japanese: the Tajimi Study. Ophthalmology

2004;111:1641-1648.

4.

Suzuki Y, Iwase A, Araie M, et al. Risk factors for open-angle

glaucoma in a Japanese population: the Tajimi Study. Ophthalmology

2006;113:1613-1617.

5.

Yamamoto T, Iwase A, Araie M, et al. The Tajimi Study report 2:

prevalence of primary angle closure and secondary glaucoma in a

Japanese population. Ophthalmology 2005;112:1661-1669.

6.

Krupin T. Physiologic basis of aqueous humor formation. The

Glaucomas 1996;251-280.

7.

Morizane Y, Morimoto N, Fujiwara A, et al. Incidence and causes of

visual impairment in Japan: the first nation-wide complete

enumeration survey of newly certified visually impaired individuals.

Jpn J Ophthalmol 2018.

8.

Ismail R, Azuara-Blanco A, Ramsay CR. Variation of clinical outcomes

used in glaucoma randomised controlled trials: a systematic review.

Br J Ophthalmol 2014;98:464-468.

9.

De Moraes CG, Liebmann JM, Levin LA. Detection and measurement

of clinically meaningful visual field progression in clinical trials for

glaucoma. Prog Retin Eye Res 2017;56:107-147.

10.

The effectiveness of intraocular pressure reduction in the treatment of

normal-tension glaucoma. Collaborative Normal-Tension Glaucoma

Study Group. Am J Ophthalmol 1998;126:498-505.

11.

Comparison of glaucomatous progression between untreated patients

with normal-tension glaucoma and patients with therapeutically

reduced intraocular pressures. Collaborative Normal-Tension

104

Glaucoma Study Group. Am J Ophthalmol 1998;126:487-497.

12.

The Advanced Glaucoma Intervention Study (AGIS): 7. The

relationship between control of intraocular pressure and visual field

deterioration.The AGIS Investigators. Am J Ophthalmol

2000;130:429-440.

13.

Chauhan BC, Mikelberg FS, Balaszi AG, et al. Canadian Glaucoma

Study: 2. risk factors for the progression of open-angle glaucoma. Arch

Ophthalmol 2008;126:1030-1036.

14.

Weinreb RN, Aung T, Medeiros FA. The pathophysiology and

treatment of glaucoma: a review. JAMA 2014;311:1901-1911.

15.

坂田 礼. 緑内障薬物治療の進歩-過去、現在、そして未来へ: 医歯薬出版

株式会社; 2017.

16.

Camras CB, Bito LZ, Eakins KE. Reduction of intraocular pressure by

prostaglandins applied topically to the eyes of conscious rabbits.

Invest Ophthalmol Vis Sci 1977;16:1125-1134.

17.

Resul B, Stjernschantz J, No K, et al. Phenyl-substituted

prostaglandins: potent and selective antiglaucoma agents. J Med

Chem 1993;36:243-248.

18.

Nomura S, Hashimoto M. [Pharmacological profiles of latanoprost

(Xalatan), a novel anti-glaucoma drug]. Nihon Yakurigaku Zasshi

2000;115:280-286.

19.

Moncada S, Vane JR. Pharmacology and endogenous roles of

prostaglandin endoperoxides, thromboxane A2, and prostacyclin.

Pharmacol Rev 1978;30:293-331.

20.

Narumiya S, Furuyashiki T. Fever, inflammation, pain and beyond:

prostanoid receptor research during these 25 years. FASEB J

2011;25:813-818.

21.

Saeki T, Ota T, Aihara M, Araie M. Effects of prostanoid EP agonists

on mouse intraocular pressure. Invest Ophthalmol Vis Sci

2009;50:2201-2208.

22.

Ocklind A. Effect of latanoprost on the extracellular matrix of the

ciliary muscle. A study on cultured cells and tissue sections. Exp Eye

Res 1998;67:179-191.

23.

Weinreb RN. Enhancement of scleral macromolecular permeability

105

with prostaglandins. Trans Am Ophthalmol Soc 2001;99:319-343.

24.

Mishima HK, Kiuchi Y, Takamatsu M, Rácz P, Bito LZ. Circadian

intraocular pressure management with latanoprost: diurnal and

nocturnal intraocular pressure reduction and increased uveoscleral

outflow. Surv Ophthalmol 1997;41 Suppl 2:S139-144.

25.

Nilsson SF, Samuelsson M, Bill A, Stjernschantz J. Increased

uveoscleral outflow as a possible mechanism of ocular hypotension

caused by prostaglandin F2 alpha-1-isopropylester in the cynomolgus

monkey. Exp Eye Res 1989;48:707-716.

26.

Alm A, Stjernschantz J. Effects on intraocular pressure and side

effects of 0.005% latanoprost applied once daily, evening or morning. A

comparison with timolol. Scandinavian Latanoprost Study Group.

Ophthalmology 1995;102:1743-1752.

27.

Aptel F, Cucherat M, Denis P. Efficacy and tolerability of

prostaglandin analogs: a meta-analysis of randomized controlled

clinical trials. J Glaucoma 2008;17:667-673.

28.

Alm A. Latanoprost in the treatment of glaucoma. Clin Ophthalmol

2014;8:1967-1985.

29.

Rácz P, Ruzsonyi MR, Nagy ZT, Bito LZ. Maintained intraocular

pressure reduction with once-a-day application of a new prostaglandin

F2 alpha analogue (PhXA41). An in-hospital, placebo-controlled study.

Arch Ophthalmol 1993;111:657-661.

30.

Camras CB, Siebold EC, Lustgarten JS, et al. Maintained reduction of

intraocular pressure by prostaglandin F2 alpha-1-isopropyl ester

applied in multiple doses in ocular hypertensive and glaucoma

patients. Ophthalmology 1989;96:1329-1336; discussion 1336-1327.

31.

Alm A. Prostaglandin derivates as ocular hypotensive agents. Prog

Retin Eye Res 1998;17:291-312.

32.

Custer PL, Kent TL. Observations on prostaglandin orbitopathy.

Ophthalmic Plast Reconstr Surg 2016;32:102-105.

33.

Bearden W, Anderson R. Trichiasis associated with prostaglandin

analog use. Ophthalmic Plast Reconstr Surg 2004;20:320-322.

34.

Sharpe ED, Reynolds AC, Skuta GL, Jenkins JN, Stewart WC. The

clinical impact and incidence of periocular pigmentation associated

106

with either latanoprost or bimatoprost therapy. Curr Eye Res

2007;32:1037-1043.

35.

Wistrand PJ, Stjernschantz J, Olsson K. The incidence and

time-course of latanoprost-induced iridial pigmentation as a function

of eye color. Surv Ophthalmol 1997;41 Suppl 2:S129-138.

36.

Stjernschantz J, Alm A. Latanoprost as a new horizon in the medical

management of glaucoma. Curr Opin Ophthalmol 1996;7:11-17.

37.

Inoue K, Shiokawa M, Wakakura M, Tomita G. Deepening of the

upper eyelid sulcus caused by 5 types of prostaglandin analogs. J

Glaucoma 2013;22:626-631.

38.

Aihara M, Shirato S, Sakata R. Incidence of deepening of the upper

eyelid sulcus after switching from latanoprost to bimatoprost. Jpn J

Ophthalmol 2011;55:600-604.

39.

Sakata R, Shirato S, Miyata K, Aihara M. Incidence of deepening of

the upper eyelid sulcus in prostaglandin-associated periorbitopathy

with a latanoprost ophthalmic solution. Eye (Lond)

2014;28:1446-1451.

40.

Sakata R, Shirato S, Miyata K, Aihara M. Incidence of deepening of

the upper eyelid sulcus on treatment with a tafluprost ophthalmic

solution. Jpn J Ophthalmol 2014;58:212-217.

41.

Filippopoulos T, Paula JS, Torun N, Hatton MP, Pasquale LR,

Grosskreutz CL. Periorbital changes associated with topical

bimatoprost. Ophthalmic Plast Reconstr Surg 2008;24:302-307.

42.

Sakata R, Shirato S, Miyata K, Aihara M. Recovery from deepening of

the upper eyelid sulcus after switching from bimatoprost to

latanoprost. Jpn J Ophthalmol 2013;57:179-184.

43.

Miki T, Naito T, Fujiwara M, et al. Effects of pre-surgical

administration of prostaglandin analogs on the outcome of

trabeculectomy. PLoS One 2017;12:e0181550.

44.

Shah M, Lee G, Lefebvre DR, et al. A cross-sectional survey of the

association between bilateral topical prostaglandin analogue use and

ocular adnexal features. PLoS One 2013;8:e61638.

45.

Krupin T, Liebmann JM, Greenfield DS, Ritch R, Gardiner S, Group

L-PGS. A randomized trial of brimonidine versus timolol in preserving

107

visual function: results from the Low-Pressure Glaucoma Treatment

Study. Am J Ophthalmol 2011;151:671-681.

46.

Anggard E, Samuelsson B. Smooth muscle stimulationg lipids in

sheep iris. The identification of prostaglandin F2a. Prostaglandins

and related factors 21. Biochem Pharmacol 1964;13:281-283.

47.

Kiriyama M, Ushikubi F, Kobayashi T, Hirata M, Sugimoto Y,

Narumiya S. Ligand binding specificities of the eight types and

subtypes of the mouse prostanoid receptors expressed in Chinese

hamster ovary cells. Br J Pharmacol 1997;122:217-224.

48.

Ota T, Aihara M, Saeki T, Narumiya S, Araie M. The IOP-lowering

effects and mechanism of action of tafluprost in prostanoid

receptor-deficient mice. Br J Ophthalmol 2007;91:673-676.

49.

Crowston JG, Lindsey JD, Morris CA, Wheeler L, Medeiros FA,

Weinreb RN. Effect of bimatoprost on intraocular pressure in

prostaglandin FP receptor knockout mice. Invest Ophthalmol Vis Sci

2005;46:4571-4577.

50.

Crowston JG, Lindsey JD, Aihara M, Weinreb RN. Effect of

latanoprost on intraocular pressure in mice lacking the prostaglandin

FP receptor. Invest Ophthalmol Vis Sci 2004;45:3555-3559.

51.

Ota T, Aihara M, Narumiya S, Araie M. The effects of prostaglandin

analogues on IOP in prostanoid FP-receptor-deficient mice. Invest

Ophthalmol Vis Sci 2005;46:4159-4163.

52.

Camras CB, Podos SM. The role of endogenous prostaglandins in

clinically-used and investigational glaucoma therapy. Prog Clin Biol

Res 1989;312:459-475.

53.

Turan-Vural E, Torun-Acar B, Acar S. Effect of ketorolac add-on

treatment on intra-ocular pressure in glaucoma patients receiving

prostaglandin analogues. Ophthalmologica 2012;227:205-209.

54.

Yousufzai SY, Ye Z, Abdel-Latif AA. Prostaglandin F2 alpha and its

analogs induce release of endogenous prostaglandins in iris and ciliary

muscles isolated from cat and other mammalian species. Exp Eye Res

1996;63:305-310.

55.

Chiba T, Kashiwagi K, Chiba N, Tsukahara S. Effect of non-steroidal

anti-inflammatory ophthalmic solution on intraocular pressure

108

reduction by latanoprost in patients with primary open angle

glaucoma or ocular hypertension. Br J Ophthalmol 2006;90:314-317.

56.

Kashiwagi K, Tsukahara S. Effect of non-steroidal anti-inflammatory

ophthalmic solution on intraocular pressure reduction by latanoprost.

Br J Ophthalmol 2003;87:297-301.

57.

Crawford KS, Kaufman PL. Dose-related effects of prostaglandin F2

alpha isopropylester on intraocular pressure, refraction, and pupil

diameter in monkeys. Invest Ophthalmol Vis Sci 1991;32:510-519.

58.

Gabelt BT, Kaufman PL. Prostaglandin F2 alpha increases

uveoscleral outflow in the cynomolgus monkey. Exp Eye Res

1989;49:389-402.

59.

Acar U, Yıldız EH, Ergintürk Acar D, et al. Posttraumatic intraocular

pressure elevation and associated factors in patients with zone I open

globe injuries. Ulus Travma Acil Cerrahi Derg 2013;19:115-118.

60.

Mao Z, Chen XB, Zhong YM, Guo XX, Liu X. Damage to the

blood-aqueous barrier in ocular blunt trauma and its association with

intraocular pressure elevation. Ophthalmic Res 2016;56:92-97.

61.

Paterson CA, Eakins KE, Paterson E, Jenkins RM, Ishikawa R. The

ocular hypertensive response following experimental acid burns in the

rabbit eye. Invest Ophthalmol Vis Sci 1979;18:67-74.

62.

Perkins ES. Prostaglandins and ocular trauma. Adv Ophthalmol

1977;34:149-152.

63.

Hayashi K, Yoshida M, Manabe SI, Yoshimura K. Prophylactic effect

of oral acetazolamide against intraocular pressure elevation after

cataract surgery in eyes with glaucoma. Ophthalmology

2017;124:701-708.

64.

Lu J, English R, Nadelstein B, et al. Comparison of topically applied

flurbiprofen or bromfenac ophthalmic solution on post-operative

ocular hypertension in canine patients following cataract surgery. Vet

Ophthalmol 2017;20:107-113.

65.

Matusow RB, Herring IP, Pickett JP, Henao-Guerrero N, Werre SR.

Effects of perioperative topical dorzolamide hydrochloride-timolol

maleate administration on incidence and severity of postoperative

ocular hypertension in dogs undergoing cataract extraction by

109

phacoemulsification. J Am Vet Med Assoc 2016;249:1040-1052.

66.

Podos SM. Effect of dipyridamole on prostaglandin-induced ocular

hypertension in rabbits. Invest Ophthalmol Vis Sci 1979;18:646-648.

67.

Sugimoto Y, Yamasaki A, Segi E, et al. Failure of parturition in mice

lacking the prostaglandin F receptor. Science 1997;277:681-683.

68.

Ushikubi F, Sugimoto Y, Ichikawa A, Narumiya S. Roles of

prostanoids revealed from studies using mice lacking specific

prostanoid receptors. Jpn J Pharmacol 2000;83:279-285.

69.

Sharif NA, Kelly CR, Crider JY, Williams GW, Xu SX. Ocular

hypotensive FP prostaglandin (PG) analogs: PG receptor subtype

binding affinities and selectivities, and agonist potencies at FP and

other PG receptors in cultured cells. J Ocul Pharmacol Ther

2003;19:501-515.

70.

Aihara M, Lindsey JD, Weinreb RN. Reduction of intraocular pressure

in mouse eyes treated with latanoprost. Invest Ophthalmol Vis Sci

2002;43:146-150.

71.

Tsuboi K, Sugimoto Y, Iwane A, Yamamoto K, Yamamoto S, Ichikawa

A. Uterine expression of prostaglandin H2 synthase in late pregnancy

and during parturition in prostaglandin F receptor-deficient mice.

Endocrinology 2000;141:315-324.

72.

Yam JC, Yuen NS, Chan CW. Bilateral deepening of upper lid sulcus

from topical bimatoprost therapy. J Ocul Pharmacol Ther

2009;25:471-472.

73.

Jayaprakasam A, Ghazi-Nouri S. Periorbital fat atrophy - an

unfamiliar side effect of prostaglandin analogues. Orbit

2010;29:357-359.

74.

Park J, Cho HK, Moon JI. Changes to upper eyelid orbital fat from use

of topical bimatoprost, travoprost, and latanoprost. Jpn J Ophthalmol

2011;55:22-27.

75.

Spiegelman BM, Flier JS. Obesity and the regulation of energy

balance. Cell 2001;104:531-543.

76.

Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin

Endocrinol Metab 2004;89:2548-2556.

77.

Spalding KL, Arner E, Westermark PO, et al. Dynamics of fat cell

110

turnover in humans. Nature 2008;453:783-787.

78.

Arner P. Fat tissue growth and development in humans. Nestle Nutr

Inst Workshop Ser 2018;89:37-45.

79.

Evans RM, Barish GD, Wang YX. PPARs and the complex journey to

obesity. Nat Med 2004;10:355-361.

80.

Fujimori K, Aritake K, Urade Y. A novel pathway to enhance

adipocyte differentiation of 3T3-L1 cells by up-regulation of

lipocalin-type prostaglandin D synthase mediated by liver X

receptor-activated sterol regulatory element-binding protein-1c. J Biol

Chem 2007;282:18458-18466.

81.

Miller CW, Casimir DA, Ntambi JM. The mechanism of inhibition of

3T3-L1 preadipocyte differentiation by prostaglandin F2alpha.

Endocrinology 1996;137:5641-5650.

82.

Choi HY, Lee JE, Lee JW, Park HJ, Jung JH. In vitro study of

antiadipogenic profile of latanoprost, travoprost, bimatoprost, and

tafluprost in human orbital preadiopocytes. J Ocul Pharmacol Ther

2012;28:146-152.

83.

Seibold LK, Ammar DA, Kahook MY. Acute effects of glaucoma

medications and benzalkonium chloride on pre-adipocyte proliferation

and adipocyte cytotoxicity in vitro. Curr Eye Res 2013;38:70-74.

84.

Reed BC, Lane MD. Insulin receptor synthesis and turnover in

differentiating 3T3-L1 preadipocytes. Proc Natl Acad Sci U S A

1980;77:285-289.

85.

Woodward DF, Krauss AH, Chen J, et al. The pharmacology of

bimatoprost (Lumigan). Surv Ophthalmol 2001;45 Suppl 4:S337-345.

86.

Hellberg MR, Sallee VL, McLaughlin MA, et al. Preclinical efficacy of

travoprost, a potent and selective FP prostaglandin receptor agonist. J

Ocul Pharmacol Ther 2001;17:421-432.

87.

Liang Y, Woodward DF, Guzman VM, et al. Identification and

pharmacological characterization of the prostaglandin FP receptor

and FP receptor variant complexes. Br J Pharmacol

2008;154:1079-1093.

88.

Tsuruma K, Tanaka Y, Shimazawa M, Mashima Y, Hara H.

Unoprostone reduces oxidative stress- and light-induced retinal cell

111

death, and phagocytotic dysfunction, by activating BK channels. Mol

Vis 2011;17:3556-3565.

89.

Yu L, Eaton AF, Yue Q, et al. Unoprostone activation of BK (KCa1.1)

channel splice variants. Biochim Biophys Acta 2015;1848:2859-2867.

90.

Cuppoletti J, Malinowska DH, Tewari KP, Chakrabarti J, Ueno R.

Unoprostone isopropyl and metabolite M1 activate BK channels and

prevent ET-1-induced [Ca²⁺]i increases in human trabecular

meshwork and smooth muscle. Invest Ophthalmol Vis Sci

2012;53:5178-5189.

91.

Green H, Kehinde O. An established preadipose cell line and its

differentiation in culture. II. Factors affecting the adipose conversion.

Cell 1975;5:19-27.

92.

Cheng JW, Cai JP, Wei RL. Meta-analysis of medical intervention for

normal tension glaucoma. Ophthalmology 2009;116:1243-1249.

93.

van der Valk R, Webers CA, Lumley T, Hendrikse F, Prins MH,

Schouten JS. A network meta-analysis combined direct and indirect

comparisons between glaucoma drugs to rank effectiveness in

lowering intraocular pressure. J Clin Epidemiol 2009;62:1279-1283.

94.

Sharif NA, Crider JY, Husain S, Kaddour-Djebbar I, Ansari HR,

Abdel-Latif AA. Human ciliary muscle cell responses to FP-class

prostaglandin analogs: phosphoinositide hydrolysis, intracellular

Ca2+ mobilization and MAP kinase activation. J Ocul Pharmacol Ther

2003;19:437-455.

95.

Takagi Y, Nakajima T, Shimazaki A, et al. Pharmacological

characteristics of AFP-168 (tafluprost), a new prostanoid FP receptor

agonist, as an ocular hypotensive drug. Exp Eye Res 2004;78:767-776.

96.

Smid SD. Role of prostaglandins and specific place in therapy of

bimatoprost in the treatment of elevated intraocular pressure and

ocular hypertension: A closer look at the agonist properties of

bimatoprost and the prostamides. Clin Ophthalmol 2009;3:663-670.

97.

Faulkner R, Sharif NA, Orr S, et al. Aqueous humor concentrations of

bimatoprost free acid, bimatoprost and travoprost free acid in cataract

surgical patients administered multiple topical ocular doses of

LUMIGAN or TRAVATAN. J Ocul Pharmacol Ther 2010;26:147-156.

112

98.

Hellberg MR, Ke TL, Haggard K, Klimko PG, Dean TR, Graff G. The

hydrolysis of the prostaglandin analog prodrug bimatoprost to

17-phenyl-trinor PGF2alpha by human and rabbit ocular tissue. J

Ocul Pharmacol Ther 2003;19:97-103.

99.

Kanamori A, Naka M, Fukuda M, Nakamura M, Negi A. Latanoprost

protects rat retinal ganglion cells from apoptosis in vitro and in vivo.

Exp Eye Res 2009;88:535-541.

100.

Kudo H, Nakazawa T, Shimura M, et al. Neuroprotective effect of

latanoprost on rat retinal ganglion cells. Graefes Arch Clin Exp

Ophthalmol 2006;244:1003-1009.

101.

Vidal L, Díaz F, Villena A, Moreno M, Campos JG, Pérez de Vargas I.

Reaction of Müller cells in an experimental rat model of increased

intraocular pressure following timolol, latanoprost and brimonidine.

Brain Res Bull 2010;82:18-24.

102.

Hernández M, Urcola JH, Vecino E. Retinal ganglion cell

neuroprotection in a rat model of glaucoma following brimonidine,

latanoprost or combined treatments. Exp Eye Res 2008;86:798-806.

103.

Uchida S, Suzuki Y, Araie M, Kashiwagi K, Otori Y, Sakuragawa N.

Factors secreted by human amniotic epithelial cells promote the

survival of rat retinal ganglion cells. Neurosci Lett 2003;341:1-4.

104.

Otori Y, Wei JY, Barnstable CJ. Neurotoxic effects of low doses of

glutamate on purified rat retinal ganglion cells. Invest Ophthalmol

Vis Sci 1998;39:972-981.

105.

Chen YN, Yamada H, Mao W, Matsuyama S, Aihara M, Araie M.

Hypoxia-induced retinal ganglion cell death and the neuroprotective

effects of beta-adrenergic antagonists. Brain Res 2007;1148:28-37.

Epub 2007 Feb 2022.

106.

Schutte B, Nuydens R, Geerts H, Ramaekers F. Annexin V binding

assay as a tool to measure apoptosis in differentiated neuronal cells. J

Neurosci Methods 1998;86:63-69.

107.

Tezel G, Yang X. Caspase-independent component of retinal ganglion

cell death, in vitro. Invest Ophthalmol Vis Sci 2004;45:4049-4059.

108.

Emre S, Gul M, Ates B, et al. Comparison of the protective effects of

prostaglandin analogues in the ischemia and reperfusion model of

113

rabbit eyes. Exp Anim 2009;58:505-513.

109.

Kurashima H, Watabe H, Sato N, Abe S, Ishida N, Yoshitomi T.

Effects of prostaglandin F(2α) analogues on endothelin-1-induced

impairment of rabbit ocular blood flow: comparison among tafluprost,

travoprost, and latanoprost. Exp Eye Res 2010;91:853-859.

110.

Akaishi T, Kurashima H, Odani-Kawabata N, Ishida N, Nakamura M.

Effects of repeated administrations of tafluprost, latanoprost, and

travoprost on optic nerve head blood flow in conscious normal rabbits.

J Ocul Pharmacol Ther 2010;26:181-186.

111.

Cantor LB, Hoop J, Wudunn D, et al. Levels of bimatoprost acid in the

aqueous humour after bimatoprost treatment of patients with cataract.

Br J Ophthalmol 2007;91:629-632.

112.

Cuppoletti J, Malinowska DH, Tewari KP, Chakrabarti J, Ueno R.

Cellular and molecular effects of unoprostone as a BK channel

activator. Biochim Biophys Acta 2007;1768:1083-1092.

113.

Hutchinson AJ, Chou CL, Israel DD, Xu W, Regan JW. Activation of

EP2 prostanoid receptors in human glial cell lines stimulates the

secretion of BDNF. Neurochem Int 2009;54:439-446.

114.

Lee EO, Shin YJ, Chong YH. Mechanisms involved in prostaglandin

E2-mediated neuroprotection against TNF-alpha: possible

involvement of multiple signal transduction and beta-catenin/T-cell

factor. J Neuroimmunol 2004;155:21-31.

115.

Jiang J, Ganesh T, Du Y, et al. Neuroprotection by selective allosteric

potentiators of the EP2 prostaglandin receptor. Proc Natl Acad Sci U S

A 2010;107:2307-2312.

116.

Liu D, Wu L, Breyer R, Mattson MP, Andreasson K. Neuroprotection

by the PGE2 EP2 receptor in permanent focal cerebral ischemia. Ann

Neurol 2005;57:758-761.

117.

McCullough L, Wu L, Haughey N, et al. Neuroprotective function of

the PGE2 EP2 receptor in cerebral ischemia. J Neurosci

2004;24:257-268.

118.

Mohan S, Narumiya S, Doré S. Neuroprotective role of prostaglandin

PGE2 EP2 receptor in hemin-mediated toxicity. Neurotoxicology

2015;46:53-59.

114

119.

Bilak M, Wu L, Wang Q, et al. PGE2 receptors rescue motor neurons

in a model of amyotrophic lateral sclerosis. Ann Neurol

2004;56:240-248.

120.

Jiang J, Dingledine R. Prostaglandin receptor EP2 in the crosshairs of

anti-inflammation, anti-cancer, and neuroprotection. Trends

Pharmacol Sci 2013;34:413-423.

121.

Echeverria V, Clerman A, Doré S. Stimulation of PGE receptors EP2

and EP4 protects cultured neurons against oxidative stress and cell

death following beta-amyloid exposure. Eur J Neurosci

2005;22:2199-2206.

122.

Ahmad AS, Zhuang H, Echeverria V, Doré S. Stimulation of

prostaglandin EP2 receptors prevents NMDA-induced excitotoxicity. J

Neurotrauma 2006;23:1895-1903.

123.

Tian X, Ji C, Luo Y, et al. PGE2-EP3 signaling pathway contributes to

protective effects of misoprostol on cerebral injury in APP/PS1 mice.

Oncotarget 2016;7:25304-25314.

124.

Pradhan SS, Salinas K, Garduno AC, et al. Anti-inflammatory and

neuroprotective effects of PGE. J Neuroimmune Pharmacol

2017;12:292-304.

125.

Akram A, Gibson CL, Grubb BD. Neuroprotection mediated by the

EP₄ receptor avoids the detrimental side effects of COX-2 inhibitors

following ischaemic injury. Neuropharmacology 2013;65:165-172.

126.

Ahmad AS, Ahmad M, de Brum-Fernandes AJ, Doré S. Prostaglandin

EP4 receptor agonist protects against acute neurotoxicity. Brain Res

2005;1066:71-77.

127.

Zhao X, Wu T, Chang CF, et al. Toxic role of prostaglandin E2 receptor

EP1 after intracerebral hemorrhage in mice. Brain Behav Immun

2015;46:293-310.

128.

Carlson NG, Rojas MA, Black JD, et al. Microglial inhibition of

neuroprotection by antagonists of the EP1 prostaglandin E2 receptor.

J Neuroinflammation 2009;6:5.

129.

Zhen G, Kim YT, Li RC, et al. PGE2 EP1 receptor exacerbated

neurotoxicity in a mouse model of cerebral ischemia and Alzheimer's

disease. Neurobiol Aging 2012;33:2215-2219.

115

130.

Kawano T, Anrather J, Zhou P, et al. Prostaglandin E2 EP1 receptors:

downstream effectors of COX-2 neurotoxicity. Nat Med

2006;12:225-229.

131.

Van Bergen NJ, Wood JP, Chidlow G, et al. Recharacterization of the

RGC-5 retinal ganglion cell line. Invest Ophthalmol Vis Sci

2009;50:4267-4272. Epub 2009 May 4214.

132.

Ohashi M, Mayama C, Ishii K, Araie M. Effects of topical travoprost

and unoprostone on optic nerve head circulation in normal rabbits.

Curr Eye Res 2007;32:743-749.

133.

Alagoz G, Gürel K, Bayer A, Serin D, Celebi S, Kukner S. A

comparative study of bimatoprost and travoprost: effect on intraocular

pressure and ocular circulation in newly diagnosed glaucoma patients.

Ophthalmologica 2008;222:88-95.

134.

Koz OG, Ozsoy A, Yarangumeli A, Kose SK, Kural G. Comparison of

the effects of travoprost, latanoprost and bimatoprost on ocular

circulation: a 6-month clinical trial. Acta Ophthalmol Scand

2007;85:838-843.

135.

Harris A, Garzozi HJ, McCranor L, Rechtman E, Yung CW, Siesky B.

The effect of latanoprost on ocular blood flow. Int Ophthalmol

2009;29:19-26.

136.

Inan UU, Ermis SS, Yücel A, Oztürk F. The effects of latanoprost and

brimonidine on blood flow velocity of the retrobulbar vessels: a

3-month clinical trial. Acta Ophthalmol Scand 2003;81:155-160.

137.

Gherghel D, Hosking SL, Cunliffe IA, Armstrong RA. First-line

therapy with latanoprost 0.005% results in improved ocular

circulation in newly diagnosed primary open-angle glaucoma patients:

a prospective, 6-month, open-label study. Eye (Lond) 2008;22:363-369.

138.

Akarsu C, Bilgili YK, Taner P, Unal B, Ergin A. Short-term effect of

latanoprost on ocular circulation in ocular hypertension. Clin Exp

Ophthalmol 2004;32:373-377.

139.

Prasanna G, Carreiro S, Anderson S, et al. Effect of PF-04217329 a

prodrug of a selective prostaglandin EP(2) agonist on intraocular

pressure in preclinical models of glaucoma. Exp Eye Res

2011;93:256-264.

116

140.

Schachar RA, Raber S, Courtney R, Zhang M. A phase 2, randomized,

dose-response trial of taprenepag isopropyl (PF-04217329) versus

latanoprost 0.005% in open-angle glaucoma and ocular hypertension.

Curr Eye Res 2011;36:809-817.

141.

Fuwa M, Toris CB, Fan S, et al. Effects of a novel selective EP2

receptor agonist, omidenepag isopropyl, on aqueous humor dynamics

in laser-induced ocular hypertensive monkeys. J Ocul Pharmacol Ther

2018;34:531-537.

142.

Iwamura R, Tanaka M, Okanari E, et al. Identification of a selective,

non-prostanoid EP2 receptor agonist for the treatment of glaucoma:

omidenepag and its prodrug omidenepag isopropyl. J Med Chem

2018;61:6869-6891.

143.

Kirihara T, Taniguchi T, Yamamura K, et al. Pharmacologic

characterization of omidenepag isopropyl, a novel selective EP2

receptor Aaonist, as an ocular hypotensive agent. Invest Ophthalmol

Vis Sci 2018;59:145-153.

144.

Berlin MS, Rowe-Rendleman C, Ahmed I, et al. EP3/FP dual receptor

agonist ONO-9054 administered morning or evening to patients with

open-angle glaucoma or ocular hypertension: results of a randomised

crossover study. Br J Ophthalmol 2016;100:843-847.

145.

Harris A, Ward CL, Rowe-Rendleman CL, et al. Ocular hypotensive

effect of ONO-9054, an EP3/FP receptor agonist: Results of a

randomized, placebo-controlled, dose escalation study. J Glaucoma

2016;25:e826-e833.

146.

Yamane S, Karakawa T, Nakayama S, et al. IOP-lowering effect of

ONO-9054, a novel dual agonist of prostanoid EP3 and FP receptors,

in monkeys. Invest Ophthalmol Vis Sci 2015;56:2547-2552.

147.

Suto F, Rowe-Rendleman CL, Ouchi T, Jamil A, Wood A, Ward CL. A

novel dual agonist of EP3 and FP receptors for OAG and OHT: Safety,

pharmacokinetics, and pharmacodynamics of ONO-9054 in healthy

volunteers. Invest Ophthalmol Vis Sci 2015;56:7963-7970.

148.

Schlötzer-Schrehardt U, Zenkel M, Nüsing RM. Expression and

localization of FP and EP prostanoid receptor subtypes in human

ocular tissues. Invest Ophthalmol Vis Sci 2002;43:1475-1487.

117

149. Aihara M, Lindsey JD, Weinreb RN. Aqueous humor dynamics in mice.

Invest Ophthalmol Vis Sci 2003;44:5168-5173.

150.

Barany EH. Simultaneous measurement of changing intraocular

pressure and outflow facility in the vervet monkey by constant

pressure infusion. Invest Ophthalmol 1964;3:135-143.

151.

Crowston JG, Aihara M, Lindsey JD, Weinreb RN. Effect of

latanoprost on outflow facility in the mouse. Invest Ophthalmol Vis

Sci 2004;45:2240-2245.

152.

Bill A. Conventional and uveo-scleral drainage of aqueous humour in

the cynomolgus monkey (Macaca irus) at normal and high intraocular

pressures. Exp Eye Res 1966;5:45-54.

153.

Pederson JE, Gaasterland DE, MacLellan HM. Uveoscleral aqueous

outflow in the rhesus monkey: importance of uveal reabsorption.

Invest Ophthalmol Vis Sci 1977;16:1008-1007.

154.

Nakajima T, Matsugi T, Goto W, et al. New fluoroprostaglandin

F(2alpha) derivatives with prostanoid FP-receptor agonistic activity

as potent ocular-hypotensive agents. Biol Pharm Bull

2003;26:1691-1695.

155.

Ota T, Murata H, Sugimoto E, Aihara M, Araie M. Prostaglandin

analogues and mouse intraocular pressure: effects of tafluprost,

latanoprost, travoprost, and unoprostone, considering 24-hour

variation. Invest Ophthalmol Vis Sci 2005;46:2006-2011.

156.

Dubiner HB, Sircy MD, Landry T, et al. Comparison of the diurnal

ocular hypotensive efficacy of travoprost and latanoprost over a

44-hour period in patients with elevated intraocular pressure. Clin

Ther 2004;26:84-91.

157.

Özyol P, Özyol E, Erdoğan BD. The Interaction of Nepafenac and

Prostaglandin Analogs in Primary Open-angle Glaucoma Patients. J

Glaucoma 2016;25:e145-149.

158.

Ota T, Aihara M, Saeki T, Narumiya S, Araie M. The effects of

prostaglandin analogues on prostanoid EP1, EP2, and EP3

receptor-deficient mice. Invest Ophthalmol Vis Sci 2006;47:3395-3399.

159.

Takamatsu M, Hotehama Y, Goh Y, Mishima HK. Localization of

prostaglandin E receptor subtypes in the ciliary body of mouse eye.

118

Exp Eye Res 2000;70:623-628.

160.

Biswas S, Bhattacherjee P, Paterson CA. Prostaglandin E2 receptor

subtypes, EP1, EP2, EP3 and EP4 in human and mouse ocular

tissues--a comparative immunohistochemical study. Prostaglandins

Leukot Essent Fatty Acids 2004;71:277-288.

161.

Ito S, Sakamoto K, Mochizuki-Oda N, et al. Prostaglandin F2 alpha

receptor is coupled to Gq in cDNA-transfected Chinese hamster ovary

cells. Biochem Biophys Res Commun 1994;200:756-762.

162.

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