ZFIN ID: ZDB-PUB-210218-10
Semaphorin 3fa Controls Ocular Vascularization From the Embryo Through to the Adult
Halabi, R., Watterston, C., Hehr, C.L., Mori-Kreiner, R., Childs, S.J., McFarlane, S.
Date: 2021
Source: Investigative ophthalmology & visual science   62: 21 (Journal)
Registered Authors:
Keywords: none
MeSH Terms:
  • Animals
  • Capillaries/growth & development*
  • Capillaries/metabolism
  • Choroid/metabolism
  • Choroid/pathology
  • DNA/genetics*
  • DNA Mutational Analysis
  • Disease Models, Animal
  • Macular Degeneration/genetics*
  • Macular Degeneration/metabolism
  • Macular Degeneration/pathology
  • Membrane Proteins/genetics*
  • Membrane Proteins/metabolism
  • Mutation*
  • Nerve Tissue Proteins/genetics*
  • Nerve Tissue Proteins/metabolism
  • Retinal Pigment Epithelium/metabolism*
  • Retinal Pigment Epithelium/pathology
  • Retinal Vessels/growth & development*
  • Retinal Vessels/metabolism
  • Zebrafish
PubMed: 33595613 Full text @ Invest. Ophthalmol. Vis. Sci.
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ABSTRACT
Pathological blood vessel growth in the eye is implicated in several diseases that result in vision loss, including age-related macular degeneration and diabetic retinopathy. The limits of current disease therapies have created the need to identify and characterize new antiangiogenic drugs. Here, we identify the secreted chemorepellent semaphorin-3fa (Sema3fa) as an endogenous anti-angiogenic in the eye.
We generated a CRISPR/Cas9 sema3fa zebrafish mutant line, sema3fa ca304/304. We assessed the retinal and choroidal vasculature in both larval and adult wild-type and sema3fa mutant zebrafish.
We find sema3fa mRNA is expressed by the ciliary marginal zone, neural retina, and retinal pigment epithelium of zebrafish larvae as choroidal vascularization emerges and the hyaloid/retinal vasculature is remodeled. The hyaloid vessels of sema3fa mutants develop appropriately but fail to remodel during the larval period, with adult mutants exhibiting a denser network of capillaries in the retinal periphery than seen in wild-type. The choroid vasculature is also defective in that it develops precociously, and aberrant, leaky sprouts are present in the normally avascular outer retina of both sema3fa ca304/304 larvae and adult fish.
Sema3fa is a key endogenous signal for maintaining an avascular retina and preventing pathologic vascularization. Furthermore, we provide a new experimentally accessible model for studying choroid neovascularization (CNV) resulting from primary changes in the retinal environment that lead to downstream vessel infiltration.
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