Near complete loss of retinal ganglion cells in the math5/brn3b double knockout elicits severe reductions of other cell types during retinal development

摘要

Retinalganglioncells(RGCs)arethefirstcelltypetodifferentiateduringretinalhistogenesis.IthasbeenpostulatedthatspecifiedRGCssubsequentlyinfluencethenumberandfateoftheremainingprogenitorstoproducetherestoftheretinalcelltypes.However,severalgeneticknockoutmodelshavearguedagainstthisdevelopmentalroleforRGCs.AlthoughitisknownthatRGCssecretecellularfactorsimplicatedincellproliferation,survival,anddifferentiation,untilnow,limitedpublicationshaveshownthatreductionsintheRGCnumbercausesignificantchangesintheseprocesses.Inthisstudy,weobservedthatMath5andBrn3bdoublenullmiceexhibitedovera99%reductioninthenumberofRGCsduringdevelopment.ThisseverereductionofRGCsisaccompaniedbyadrasticlossinthenumberofallotherretinalcelltypesthatwasneverseenbefore.UnlikeBrn3bnullorMath5nullanimals,micenullforbothalleleslackanopticnerveandhavesevereretinaldysfunction.ResultsofthisstudysupportthehypothesisthatRGCsplayapivotalroleinthelatephaseofmammalianretinadevelopment./p/div