title: Neuron-specific TGF-beta signaling deficiency results in retinal detachment and cataracts in mice.
abstract: We generated a mouse model (cKO) with a conditional deletion of TGF-beta signaling in the retinal neurons by crossing TGF-beta receptor I (TGF-beta RI) floxed mice with nestin-Cre mice. Almost all of the newborn cKO mice had retinal detachment at the retinal pigment epithelium (RPE)/photoreceptor layer junction of the neurosensory retina (NSR). The immunostaining for chondroitin-6-sulfate showed a very weak reaction in cKO mice in contrast to intense staining in the photoreceptor layer in wild-type mice. Macroscopic cataracts, in one or both eyes, were observed in 50% of the mice by 6 months of age, starting as early as the first month after birth. The cKO mouse model demonstrates that the TGF-beta signaling deficiency in retinal cells leads to decreased levels of chondroitin sulfate proteoglycan in the retinal interphotoreceptor matrix. This in turn causes retinal detachment due to the loss of adhesion of the NSR to RPE.
authors.affiliation: Functional Genomics Section, Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and Craniofacial Research, Bethesda, MD 20892, USA.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Honjo
authors.forename: Chandrasekharam N
authors.initials: CN
authors.lastname: Nagineni
authors.forename: Jonas
authors.initials: J
authors.lastname: Larsson
authors.forename: Seshagiri R
authors.initials: SR
authors.lastname: Nandula
authors.forename: John J
authors.initials: JJ
authors.lastname: Hooks
authors.forename: Chi-Chao
authors.initials: CC
authors.lastname: Chan
authors.forename: Stefan
authors.initials: S
authors.lastname: Karlsson
authors.forename: Ashok B
authors.initials: AB
authors.lastname: Kulkarni
mesh_terms: D000818:Animals; D002386:Cataract / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D012163:Retinal Detachment / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D015398:Signal Transduction / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000172:deficiency* / Q000235:genetics
chemical_list: D016212:Transforming Growth Factor beta