Retinal proliferation response in the buphthalmic zebrafish, bugeye
- Authors
- Sherpa, T., Hunter, S.S., Frey, R.A., Robison, B.D., and Stenkamp, D.L.
- ID
- ZDB-PUB-110706-13
- Date
- 2011
- Source
- Experimental Eye Research 93(4): 424-36 (Journal)
- Registered Authors
- Frey, Ruth, Stenkamp, Deborah L.
- Keywords
- zebrafish, retina, retinal ganglion cell, regeneration, glaucoma, buphthalmos
- MeSH Terms
-
- Animals
- Disease Models, Animal*
- Animals, Genetically Modified
- Hydrophthalmos/genetics
- Hydrophthalmos/pathology*
- Stress, Mechanical
- Zebrafish/genetics
- Intraocular Pressure
- Low Density Lipoprotein Receptor-Related Protein-2/genetics
- HSP27 Heat-Shock Proteins/metabolism
- Gene Expression Regulation/physiology
- Neuroglia/pathology
- In Situ Nick-End Labeling
- Eye Abnormalities/genetics
- Eye Abnormalities/pathology*
- Vision Disorders/genetics
- Vision Disorders/pathology
- Regeneration/physiology
- Fluorescent Antibody Technique, Indirect
- Cell Proliferation*
- Cell Count
- Optic Disk/abnormalities
- Retinal Ganglion Cells/pathology*
- PubMed
- 21723280 Full text @ Exp. Eye. Res.
The zebrafish retina regenerates in response to acute retinal lesions, replacing damaged neurons with new neurons. In this study we test the hypothesis that chronic stress to inner retinal neurons also triggers a retinal regeneration response in the bugeye zebrafish. Mutations in the lrp2 gene in zebrafish are associated with a progressive eye phenotype (bugeye) that models several risk factors for human glaucoma including buphthalmos (enlarged eyes), elevated intraocular pressure (IOP), and upregulation of genes related to retinal ganglion cell pathology. The retinas of adult bugeye zebrafish showed high rates of ongoing proliferation which resulted in the production of a small number of new retinal neurons, particularly photoreceptors. A marker of mechanical cell stress, Hsp27, was strongly expressed in inner retinal neurons and glia of bugeye retinas. The more enlarged eyes of individual bugeye zebrafish showed disrupted retinal lamination, and a persistent reduced density of neurons in the ganglion cell layer (GCL), although total numbers of GCL neurons were higher than in control eyes. Despite the presence of a proliferative response to damage, the adult bugeye zebrafish remained behaviorally blind. These findings suggest the existence of an unsuccessful regenerative response to a persistent pathological condition in the bugeye zebrafish.