Systemic exposure to UVB is sufficient to induce AMD: Characterization of a Novel Animal Model

Abstract

Purpose : Exposure to ultraviolet light is linked to age-related macular degeneration (AMD) and is thought to occur via direct exposure of the retina to UVB radiation. The purpose of this study is to evaluate whether skin exposure to UVB alone is sufficient to induce features of AMD in a rodent model.

Methods : C57Bl6/J male mice (9-13 weeks) were exposed to UVB irradiation (200 mi/cm²) three times weekly for two weeks while the head and eyes were shielded to prevent direct exposure of the eyes to UVB irradiation. Age-matched male C57Bl6/J male mice maintained in a normal 24-hour light/dark cycle vivarium without UVB exposure were used as controls. Baseline and post-UVB exposure visual function was assessed using scotopic and photopic electroretinogram (ERG) and optical coherence tomography (SD-OCT, Bioptigen Envisu-R2200). Following exposure to UVB irradiation, choroidal neovascularization was induced using a diode laser (240mJ duration 70 ms) with 4 lesions per eye within a 2-disc diameter from the optic disc. Retinal thickness and CNV area (longest length x width) was measured using OCT five days after laser injury. Finally, the eye globes collected and fixate tissue sectioning of one eye and western blot to the other eye for each mouse using MITF, TRPM1, TRPM3 and Melan A.

Results : UVB irradiation to the skin but not the head and eyes resulted in significant thinning of the retinal pigmented epithelium and choroid and lower scotopic and photopic B wave (ERG) when compared with control mice. Laser-injury to the retina/choroid resulted in much larger choroidal neovascularization in UVB-exposed mice when compared with control mice. UVB exposure of the skin but not the head/eyes resulted in increased expression of Microphthalmia-associated transcription factor (MITF), Transient receptor potential cation channel subfamily M member 3, and melanin A in the retina/choroid suggesting that direct exposure of the retina/choroid to UV irradiation is not necessary to induce AMD in a rodent model.

Conclusions : Skin exposure to UVB is sufficient to induce AMD-like changes in a rodent model and suggests that blocking exposure of the skin to UVB via sunscreens may impact the incidence of AMD and chorioretinal atrophy

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