Challenges and Opportunities in P450 Research on the Eye

Overview

Journal Drug Metab Dispos

Specialty Pharmacology

Date 2023 Mar 13

PMID 36914277

Authors

Irina A Pikuleva

Affiliations

Soon will be listed here.

Abstract

Of the 57 cytochrome P450 enzymes found in humans, at least 30 have ocular tissues as an expression site. Yet knowledge of the roles of these P450s in the eye is limited, in part because only very few P450 laboratories expanded their research interests to studies of the eye. Hence the goal of this review is to bring attention of the P450 community to the eye and encourage more ocular studies. This review is also intended to be educational for eye researchers and encourage their collaborations with P450 experts. The review starts with a description of the eye, a fascinating sensory organ, and is followed by sections on ocular P450 localizations, specifics of drug delivery to the eye, and individual P450s, which are grouped and presented based on their substrate preferences. In sections describing individual P450s, available eye-relevant information is summarized and concluded by the suggestions on the opportunities in ocular studies of the discussed enzymes. Potential challenges are addressed as well. The conclusion section outlines several practical suggestions on how to initiate eye-related research. SIGNIFICANCE STATEMENT: This review focuses on the cytochrome P450 enzymes in the eye to encourage their ocular investigations and collaborations between P450 and eye researchers.

References

El Matri K, Falfoul Y, Habibi I, Chebil A, Schorderet D, El Matri L . Macular Dystrophy with Bilateral Macular Telangiectasia Related to the CYP2U1 Pathogenic Variant Assessed with Multimodal Imaging Including OCT-Angiography. Genes (Basel). 2021; 12(11). PMC: 8618989. DOI: 10.3390/genes12111795. View

Cenedella R, Fleschner C . Cholesterol biosynthesis by the cornea. Comparison of rates of sterol synthesis with accumulation during early development. J Lipid Res. 1989; 30(7):1079-84. View

Branch R, Adedoyin A, Frye R, Wilson J, Romkes M . In vivo modulation of CYP enzymes by quinidine and rifampin. Clin Pharmacol Ther. 2000; 68(4):401-11. DOI: 10.1067/mcp.2000.110561. View

Zhang T, Xiang C, Gale D, Carreiro S, Wu E, Zhang E . Drug transporter and cytochrome P450 mRNA expression in human ocular barriers: implications for ocular drug disposition. Drug Metab Dispos. 2008; 36(7):1300-7. DOI: 10.1124/dmd.108.021121. View

Lee J, Jiao X, Hejtmancik J, Chader G . Identification, isolation, and characterization of a 32-kDa fatty acid-binding protein missing from lymphocytes in humans with Bietti crystalline dystrophy (BCD). Mol Genet Metab. 1998; 65(2):143-54. DOI: 10.1006/mgme.1998.2723. View

Oak A, Messinger J, Curcio C . Subretinal drusenoid deposits: further characterization by lipid histochemistry. Retina. 2014; 34(4):825-6. DOI: 10.1097/IAE.0000000000000121. View

Cenedella R . Cholesterol and cataracts. Surv Ophthalmol. 1996; 40(4):320-37. DOI: 10.1016/s0039-6257(96)82007-8. View

Li N, Zhou Y, Du L, Wei M, Chen X . Overview of Cytochrome P450 1B1 gene mutations in patients with primary congenital glaucoma. Exp Eye Res. 2011; 93(5):572-9. DOI: 10.1016/j.exer.2011.07.009. View

Zhang X, Alhasani R, Zhou X, Reilly J, Zeng Z, Strang N . Oxysterols and retinal degeneration. Br J Pharmacol. 2021; 178(16):3205-3219. DOI: 10.1111/bph.15391. View

10.

Li A, Jiao X, Munier F, Schorderet D, Yao W, Iwata F . Bietti crystalline corneoretinal dystrophy is caused by mutations in the novel gene CYP4V2. Am J Hum Genet. 2004; 74(5):817-26. PMC: 1181977. DOI: 10.1086/383228. View

11.

Martinez-Gil N, Flores-Bellver M, Atienzar-Aroca S, Lopez-Malo D, Urdaneta A, Sancho-Pelluz J . CYP2E1 in the Human Retinal Pigment Epithelium: Expression, Activity, and Induction by Ethanol. Invest Ophthalmol Vis Sci. 2015; 56(11):6855-63. DOI: 10.1167/iovs.14-16291. View

12.

Nakano M, Kelly E, Wiek C, Hanenberg H, Rettie A . CYP4V2 in Bietti's crystalline dystrophy: ocular localization, metabolism of ω-3-polyunsaturated fatty acids, and functional deficit of the p.H331P variant. Mol Pharmacol. 2012; 82(4):679-86. PMC: 3463217. DOI: 10.1124/mol.112.080085. View

13.

Stoilov I . Cytochrome P450s: coupling development and environment. Trends Genet. 2001; 17(11):629-32. DOI: 10.1016/s0168-9525(01)02444-1. View

14.

Thomas A, Henry J . Retinoic acid regulation by CYP26 in vertebrate lens regeneration. Dev Biol. 2014; 386(2):291-301. PMC: 3939837. DOI: 10.1016/j.ydbio.2013.12.036. View

15.

Lee J, Fuda H, Javitt N, Strott C, Rodriguez I . Expression and localization of sterol 27-hydroxylase (CYP27A1) in monkey retina. Exp Eye Res. 2006; 83(2):465-9. PMC: 2806429. DOI: 10.1016/j.exer.2005.11.018. View

16.

Nakano M, Lockhart C, Kelly E, Rettie A . Ocular cytochrome P450s and transporters: roles in disease and endobiotic and xenobiotic disposition. Drug Metab Rev. 2014; 46(3):247-60. PMC: 4676416. DOI: 10.3109/03602532.2014.921190. View

17.

Xie Q, Zhang Q, Zhang Y, Su T, Gu J, Kaminsky L . Induction of mouse CYP2J by pyrazole in the eye, kidney, liver, lung, olfactory mucosa, and small intestine, but not in the heart. Drug Metab Dispos. 2000; 28(11):1311-6. View

18.

Meaney S, Heverin M, Panzenboeck U, Ekstrom L, Axelsson M, Andersson U . Novel route for elimination of brain oxysterols across the blood-brain barrier: conversion into 7alpha-hydroxy-3-oxo-4-cholestenoic acid. J Lipid Res. 2007; 48(4):944-51. DOI: 10.1194/jlr.M600529-JLR200. View

19.

Nelson D, Zeldin D, Hoffman S, Maltais L, Wain H, Nebert D . Comparison of cytochrome P450 (CYP) genes from the mouse and human genomes, including nomenclature recommendations for genes, pseudogenes and alternative-splice variants. Pharmacogenetics. 2004; 14(1):1-18. DOI: 10.1097/00008571-200401000-00001. View

20.

Baulieu E . Neurosteroids: of the nervous system, by the nervous system, for the nervous system. Recent Prog Horm Res. 1997; 52:1-32. View