Cone Photoreceptor Degeneration and Neuroinflammation in the Zebrafish Bardet-Biedl Syndrome 2 (bbs2) Mutant Does Not Lead to Retinal Regeneration
Year: 2020
Type: article
Abstract: Bardet-Biedl syndrome (BBS) is a heterogeneous and pleiotropic autosomal recessive disorder characterized by obesity, retinal degeneration, polydactyly, renal dysfunction, and mental retardation. BBS results from defects in primary and sensory cilia. Mutations in 21 genes have been linked to BBS and proteins encoded by 8 of these genes form a multiprotein complex termed the BBSome. Mutations inBBS2, a component of the BBSome, result in BBS as well as non-syndromic retinal degeneration in humans and rod degeneration in mice, but the role of BBS2 in cone photoreceptor survival is not clear. We used zebrafishbbs2–/–mutants to better understand how loss ofbbs2leads to photoreceptor degeneration. Zebrafishbbs2–/–mutants exhibited impaired visual function as larvae and adult zebrafish underwent progressive cone photoreceptor degeneration. Cone degeneration was accompanied by increased numbers of activated microglia, indicating an inflammatory response. Zebrafish exhibit a robust ability to regenerate lost photoreceptors following retinal damage, yet cone degeneration and inflammation was insufficient to trigger robust Müller cell proliferation. In contrast, high intensity light damage stimulated Müller cell proliferation and photoreceptor regeneration in both wild-type andbbs2–/–mutants, although thebbs2–/–mutants could only restore cones to pre-damaged densities. In summary, these findings suggest that cone degeneration leads to an inflammatory response in the retina and that BBS2 is necessary for cone survival. The zebrafishbbs2mutant also represents an ideal model to identify mechanisms that will enhance retinal regeneration in degenerating diseases.
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,950
Awards: G1540503468, G2174653459, G5674470148, Stimulating Retina Regeneration from Muller Cells in Progressive Retinal Degenerations, The Role of microRNAs in Photoreceptor Outer Segment Morphogenesis, G6196185825, Cilia Assembly and Transport in Photoreceptor Cells, G7087067255, G769556647, G7871533118, G9000162082, G9000177402, G9000227827, NEI Center Core Grant for Vision Research
OpenAlex ID: W3108260955