Neuron-specific TGF-β signaling deficiency results in retinal detachment and cataracts in mice

Yasuyuki Honjo, Chandrasekharam N. Nagineni, Jonas Larsson, Seshagiri R. Nandula, John J. Hooks, Chi Chao Chan, Stefan Karlsson, Ashok B. Kulkarni

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

We generated a mouse model (cKO) with a conditional deletion of TGF-β signaling in the retinal neurons by crossing TGF-β receptor I (TGF-β 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-β 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.

Original languageEnglish (US)
Pages (from-to)418-422
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume352
Issue number2
DOIs
StatePublished - Jan 12 2007

Bibliographical note

Funding Information:
We thank Dr. Ryoichiro Kagayama, Institute of Virus Research, Kyoto University, Japan, for providing nestin-Cre mice. This research was supported [in part] by the Intramural Research Program of the National Institutes of Dental and Craniofacial Research and National Eye Institute, National Institutes of Health. Appendix A

Keywords

  • Cataracts
  • Chondroitin-6-sulfate
  • Cre-lox P system
  • Extracellular matrix
  • Retina
  • Retinal detachment
  • Retinal pigment epithelium
  • TGF-β
  • TGF-β receptor I

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