LC-MSMS on mouse retina to investigate photoreceptor degeneration

ABSTRACT: Intraocular anti-VEGFA injections are frequently used to counteract neovascularization in diseases such as the neovascular (wet) form of age-related macular degeneration (AMD) or proliferative diabetic retinopathy. However, in the clinical context, patients with atrophic (dry) and wet AMD in the same eye will receive anti-VEGFA injections, but there are reports that this severely promotes the development of atrophic areas in dry AMD. To study this, we used mice with a tamoxifen-dependent deletion of Vegfr2 in the eye (Vegfr2Δeye) and the light damage model to induce degeneration of photoreceptors and to mimic certain aspects of dry AMD. We examined retinal morphology and function, the degree of photoreceptor degeneration, as well as alterations of the retinal proteome. While, steady-state retinal morphology and function was not altered due to VEGF signaling deficiency, light-induced photoreceptor degeneration was drastically exacerbated in VEGF signaling deficient retinae concomitant with attenuated activation of the AKT kinase pathway. Furthermore, using single nuclei RNA sequencing data, we show that in humans Vegfr2 is predominantly expressed in macroglia cells of healthy retinae, dry and wet AMD patients, suggesting a VEGF-dependent neuroprotective crosstalk from macroglia cells to photoreceptors which might pose promising therapeutic options to attenuate photoreceptor degeneration in humans. Yet, our data also indicate that the use of anti-VEGF therapy should be carefully considered in the presence of neurodegenerative comorbidities, since deletion of VEGF signaling dramatically promoted neurodegeneration

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): R1 Photoreceptor Cell, Retina

DISEASE(S): Age Related Macular Degeneration 1

SUBMITTER: Christine von Toerne  

LAB HEAD: Barbara M. Braunger

PROVIDER: PXD066263 | Pride | 2026-06-15

REPOSITORIES: Pride