Editors Selection (IGR: 10-2) | International Glaucoma Review #1803

Editors Selection IGR 10-2

Basic Science: Gene Expression and Sex

Comment by Louis Pasquale on:

74657 Retinal gene expression responses to aging are sexually divergent, Du M; Mangold CA; Bixler GV et al., Molecular Vision, 2017; 23: 707-717

Age and sex significantly influence the risk for developing glaucoma and other age-related blinding conditions, such as age-related macular degeneration, yet pathophysiology of eye aging is not well understood.¹

Pathophysiology of eye aging is not well understood

Likewise, it is not known if an aging process differs between men and women. As an age-related neurodegeneration, primary open-angle glaucoma (POAG) is also considered accelerated optic nerve aging because the glaucomatous optic nerve shares both immunohistochemical and clinical characteristics, similar to aging. Evidently, they both exhibit reactive products from an oxidative stress² and a characteristic pattern of neuroretinal rim loss in the inferotemporal region.³ In addition, the risk of POAG in women is affected not only by chronological age, but also by advancing reproductive age and lifetime exposure to estrogens.⁴ Recognized the critical effects of the biological sex on aging eye conditions, such as POAG and retinal diseases, Du et al. investigated sex differences in aging. By comparing retinal gene expression responses in female and male C57BL/6JN mice, aged 3 and 24 months, they demonstrated retinal sex differences throughout a mouse lifespan. Notably, while common gene expression exists, as anticipated, the gene expression responses to aging indeed predominantly differ between male and female mice. They further hypothesized that the sexually divergent gene expression throughout life is likely the effects of sex hormones on the retina. Specifically, sex hormones could potentially affect cell function and gene regulation through estrogen, androgen, and non-estrogen receptors within the retina and the retinal pigment epithelium. This observed sexually divergent gene expression responses to aging certainly warrants further investigations. Most importantly, these findings highlight an urgent need to include both sexes in pre-clinical and clinical research. Considering both sexes in aging research will subsequently lead to better understanding of likely interactions between the effects of age and sex on various age-related blinding conditions.

References

Vajaranant TS, Pasquale LR. Estrogen deficiency accelerates aging of the optic nerve. Menopause (New York, N.Y. Aug 2012;19(8):942-947.
Tezel G, Luo C, Yang X. Accelerated aging in glaucoma: immunohistochemical assessment of advanced glycation end products in the human retina and optic nerve head. Investigative ophthalmology & visual science. Mar 2007;48(3):1201-1211.
See JL, Nicolela MT, Chauhan BC. Rates of neuroretinal rim and peripapillary atrophy area change: a comparative study of glaucoma patients and normal controls. Ophthalmology. May 2009;116(5):840-847.
Pasquale LR, Rosner BA, Hankinson SE, Kang JH. Attributes of female reproductive aging and their relation to primary open-angle glaucoma: a prospective study. Journal of glaucoma. Oct-Nov 2007;16(7):598-605.

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