Lens-specific expression of PDGF-A in transgenic mice results in retinal astrocytic hamartomas

Invest Ophthalmol Vis Sci. 1996 Nov;37(12):2455-66.

Abstract

Purpose: To investigate the possibility that platelet-derived growth factor (PDGF) might regulate aspects of mouse retinal development in vivo.

Methods: In situ hybridization was used to study the expression patterns of PDGF-A and PDGF-B and their receptors during normal mouse eye development. Transgenic mice that express human PDGF-A in the lens under the control of alpha A-crystallin promoter were generated by pronuclear microinjection. The effects of PDGF overexpression on eye development were analyzed by ocular histology, immunohistochemistry and in situ hybridizations.

Results: The PDGF genes are expressed by cells in close contact with retinal astrocytes. The PDGF-A messenger RNA is upregulated in the retinal ganglion neurons after birth, and PDGF-B is expressed by the blood vessel cells in the hyaloid vasculature. The authors found that lens-specific expression of PDGF-A in the eye can induce hyperplasia of retinal astrocytes, which express PDGF-alpha receptor (PDGF-alpha R) during development. The retinal alterations in the PDGF-A transgenic mice closely resemble the retinal astrocytic hamartomas found in human tuberous sclerosis (TSC) disease.

Conclusions: These findings suggest that proliferation of retinal astrocytes is regulated by PDGF during normal eye development. The authors speculate that proliferation of retinal astrocytes is mediated through a PDGF signaling pathway, which may involve the TSC gene product.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Astrocytes / pathology*
  • Cell Division
  • Crystallins / genetics
  • Female
  • Gene Expression*
  • Hamartoma / etiology*
  • Hamartoma / pathology
  • Immunoenzyme Techniques
  • In Situ Hybridization
  • Lens, Crystalline / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred ICR
  • Mice, Transgenic
  • Platelet-Derived Growth Factor / biosynthesis*
  • Platelet-Derived Growth Factor / genetics
  • Protein-Tyrosine Kinases / biosynthesis
  • Protein-Tyrosine Kinases / genetics
  • Proto-Oncogene Proteins / biosynthesis
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-sis
  • RNA, Messenger / metabolism
  • Receptor, Platelet-Derived Growth Factor alpha
  • Receptors, Platelet-Derived Growth Factor / metabolism
  • Retinal Diseases / etiology*
  • Retinal Diseases / pathology
  • Transfection
  • Up-Regulation

Substances

  • Crystallins
  • Platelet-Derived Growth Factor
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-sis
  • RNA, Messenger
  • platelet-derived growth factor A
  • Protein-Tyrosine Kinases
  • Receptor, Platelet-Derived Growth Factor alpha
  • Receptors, Platelet-Derived Growth Factor