Melanopsin: A potential therapeutic target for retinopathy of prematurity

Abstract

Purpose : Melanopsin (OPN4) is the photopigment of light-sensitive retinal ganglion cells. It is maximally sensitive to blue light, active early in development, and implicated in the timing of ocular vascular development. This study was conducted to determine if melanopsin influences the development and severity of oxygen-induced retinopathy (OIR), an animal model of retinopathy of prematurity (ROP).

Methods : Wild type C57BL/6J and Opn4 mutant mice were exposed to either room air or 75-76% oxygen over postnatal (P) days 7-12 under normal colony room conditions. Oxygen-treated mice were returned to room air at P12 and mice were euthanized at P17 or at 7 weeks of age. To test involvement of blue light-sensitive melanopsin in retinopathy, other C57BL/6J mice underwent 5 days of hyperoxia, then were maintained in room air but exposed to either normal light, blue-deficient light, or blue-enhanced light over P12-17. Vasculature of retinal flatmounts was labeled with FL-1171 (Vector Laboratories) and analyzed for areas of vaso-obliteration (VO) and neovascularization (NV). Dark-adapted electroretinogram (ERG) recordings were collected at P46.

Results : Mice of all genotypes developed retinopathy by P17 following oxygen treatment, but mice with a homozygous knockout of the melanopsin gene (Opn4^-/-) showed more retinopathy than either wild type (Opn4^+/+) or heterozygous mice (Opn4^+/-). Retinas of oxygen-treated Opn4^-/- mice had significantly greater areas of VO and NV in comparison to oxygen-treated Opn4^+/- or Opn4^+/+ mice when measured at P17 (p<0.01). Dark-adapted ERG recordings at P46 showed significantly reduced ERG a-wave amplitudes in oxygen-treated mice compared to those maintained in room air. ERG a-wave amplitudes of oxygen-treated Opn4^-/- mice were significantly lower than those of oxygen-treated Opn4^+/+ mice (p<0.05). Oxygen-treated C57BL/6J mice exposed to blue-deficient light from P12-P17 showed greater NV (p<0.01) and VO (p<0.01) compared to those maintained in colony room light, phenocopying the effect of Opn4 knockout. In contrast, blue-enhanced light exposure significantly lowered VO in oxygen-treated wild type animals compared to those in colony room light (p=0.01).

Conclusions : Melanopsin influences the pathogenesis of OIR, suggesting that activation of melanopsin with blue light may provide a non-invasive treatment to reduce the development of ROP in infants.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.