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Survival and remodeling of melanopsin cells during retinal dystrophy

Published online by Cambridge University Press:  28 April 2008

ANTHONY A. VUGLER ,
MA'AYAN SEMO ,
ANNA JOSEPH  and
GLEN JEFFERY
ANTHONY A. VUGLER*
Affiliation:
Institute of Ophthalmology, University College London, London, United Kingdom
MA'AYAN SEMO
Affiliation:
Institute of Ophthalmology, University College London, London, United Kingdom
ANNA JOSEPH
Affiliation:
Institute of Ophthalmology, University College London, London, United Kingdom
GLEN JEFFERY
Affiliation:
Institute of Ophthalmology, University College London, London, United Kingdom
*
Address correspondence and reprint requests to: Anthony Vugler, UCL-Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, United Kingdom. E-mail: a.vugler@ucl.ac.uk
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Abstract

The melanopsin positive, intrinsically photosensitive retinal ganglion cells (ipRGCs) of the inner retina have been shown to send wide-ranging projections throughout the brain. To investigate the response of this important cell type during retinal dystrophy, we use the Royal College of Surgeons (RCS) dystrophic rat, a major model of retinal degeneration. We find that ipRGCs exhibit a distinctive molecular profile that remains unaltered during early stages of outer retinal pathology (15 weeks of age). In particular, these cells express βIII tubulin, α-acetylated tubulin, and microtubule-associated proteins (MAPs), while remaining negative for other RGC markers such as neurofilaments, calretinin, and parvalbumin. By 14 months of age, melanopsin positive fibers invade ectopic locations in the dystrophic retina and ipRGC axons/dendrites become distorted (a process that may involve vascular remodeling). The morphological abnormalities in melanopsin processes are associated with elevated immunoreactivity for MAP1b and a reduction in α-acetylated tubulin. Quantification of ipRGCs in whole mounts reveals reduced melanopsin cell number with increasing age. Focusing on the retinal periphery, we find a significant decline in melanopsin cell density contrasted by a stability of melanopsin positive processes. In addition to these findings, we describe for the first time, a distinct plexus of melanopsin processes in the far peripheral retina, a structure that is coincident with a short wavelength opsin cone-enriched rim. We conclude that some ipRGCs are lost in RCS dystrophic rats as the disease progresses and that this loss may involve vascular remodeling. However, a significant number of melanopsin positive cells survive into advanced stages of retinal degeneration and show indications of remodeling in response to pathology. Our findings underline the importance of early intervention in human retinal disease in order to preserve integrity of the inner retinal photoreceptive network.

Keywords

RCS dystrophic ratMelanopsinBeta III tubulinMAPS opsin cone rich rim
Type
Research Article
Information
Visual Neuroscience , Volume 25 , Issue 2 , March 2008 , pp. 125 - 138
Copyright
Copyright © Cambridge University Press 2008

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