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ZFIN ID: ZDB-PUB-110706-13
Retinal proliferation response in the buphthalmic zebrafish, bugeye
Sherpa, T., Hunter, S.S., Frey, R.A., Robison, B.D., and Stenkamp, D.L.
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
  • Animals, Genetically Modified
  • Cell Count
  • Cell Proliferation*
  • Disease Models, Animal*
  • Eye Abnormalities/genetics
  • Eye Abnormalities/pathology*
  • Fluorescent Antibody Technique, Indirect
  • Gene Expression Regulation/physiology
  • HSP27 Heat-Shock Proteins/metabolism
  • Hydrophthalmos/genetics
  • Hydrophthalmos/pathology*
  • In Situ Nick-End Labeling
  • Intraocular Pressure
  • Low Density Lipoprotein Receptor-Related Protein-2/genetics
  • Neuroglia/pathology
  • Optic Disk/abnormalities
  • Regeneration/physiology
  • Retinal Ganglion Cells/pathology*
  • Stress, Mechanical
  • Vision Disorders/genetics
  • Vision Disorders/pathology
  • Zebrafish/genetics
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.