Metabolic changes and retinal remodeling in Heterozygous CRX mutant cats (CRX RDY/+ ).

Autor: Occelli LM; Small Animal Clinical Sciences, Michigan State University, 736 Wilson Road, East Lansing, MI, USA. Electronic address: l_occelli@yahoo.fr., Jones BW; Ophthalmology, Moran Eye Center, University of Utah, Salt Lake City, UT, USA. Electronic address: bryan.jones@m.cc.utah.edu., Cervantes TJ; Small Animal Clinical Sciences, Michigan State University, 736 Wilson Road, East Lansing, MI, USA. Electronic address: taylorj.cervantes@gmail.com., Petersen-Jones SM; Small Animal Clinical Sciences, Michigan State University, 736 Wilson Road, East Lansing, MI, USA. Electronic address: peter315@msu.edu.
Jazyk: angličtina
Zdroj: Experimental eye research [Exp Eye Res] 2023 Oct; Vol. 235, pp. 109630. Date of Electronic Publication: 2023 Aug 23.
DOI: 10.1016/j.exer.2023.109630
Abstrakt: CRX is a transcription factor essential for normal photoreceptor development and survival. The CRX Rdy cat has a naturally occurring truncating mutation in CRX and is a large animal model for dominant Leber congenital amaurosis. This study investigated retinal remodeling that occurs as photoreceptors degenerate. CRX Rdy/+ cats from 6 weeks to 10 years of age were investigated. In vivo structural changes of retinas were analyzed by fundus examination, confocal scanning laser ophthalmoscopy and spectral domain optical coherence tomography. Histologic analyses included immunohistochemistry for computational molecular phenotyping with macromolecules and small molecules. Affected cats had a cone-led photoreceptor degeneration starting in the area centralis. Initially there was preservation of inner retinal cells such as bipolar, amacrine and horizontal cells but with time migration of the deafferented neurons occurred. Early in the process of degeneration glial activation occurs ultimately resulting in formation of a glial seal. With progression the macula-equivalent area centralis developed severe atrophy including loss of retinal pigmentary epithelium. Microneuroma formation occured in advanced stages as more marked retinal remodeling occurred. This study indicates that retinal degeneration in the Crx Rdy/+ cat retina follows the progressive, phased revision of retina that have been previously described for retinal remodeling. These findings suggest that therapy dependent on targeting inner retinal cells may be useful in young adults with preserved inner retinas prior to advanced stages of retinal remodeling and neuronal cell loss.
(Copyright © 2023. Published by Elsevier Ltd.)
Databáze: MEDLINE
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