Exaggerated eye growth in IRBP-deficient mice in early development

Invest Ophthalmol Vis Sci. 2011 Jul 29;52(8):5804-11. doi: 10.1167/iovs.10-7129.

Abstract

Purpose: Because interphotoreceptor retinoid-binding protein (IRBP) is expressed before being needed in its presumptive role in the visual cycle, we tested whether it controls eye growth during development.

Methods: The eyes of congenic IRBP knockout (KO) and C57BL/6J wild-type (WT) mice ranging in age from postnatal day (P)2 to P440 were compared by histology, laser micrometry, cycloplegic photorefractions, and partial coherence interferometry.

Results: The size and weight of IRBP KO mouse eyes were greater than those of the WT mouse, even before eye-opening. Excessive ocular enlargement started between P7 and P10, with KO retinal arc lengths becoming greater compared with WT from P10 through P30 (18%; P < 0.01). The outer nuclear layer (ONL) of KO retinas became 20% thinner between P12 to P25, and progressed to 38% thinner at P30. At P30, there were 30% fewer cones per vertical section in KO than in WT retinas. Bromodeoxyuridine (BrdU) labeling indicated the same number of retinal cells were born in KO and WT mice. A spike in apoptosis was observed in KO outer nuclear layer at P25. These changes in size were accompanied by a large decrease in hyperopic refractive error, which reached -4.56 ± 0.70 diopters (D) versus +9.98 ± 0.993 D (mean ± SD) in WT, by postnatal day 60 (P60). CONCLUSIONS; In addition to its role in the visual cycle, IRBP is needed for normal eye development. How IRBP mediates ocular development is unknown.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Eye / anatomy & histology*
  • Eye / growth & development*
  • Eye Abnormalities / genetics*
  • Eye Abnormalities / pathology*
  • Eye Proteins / genetics*
  • Female
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Confocal
  • Microscopy, Interference
  • Organ Size / physiology
  • Refractive Errors / pathology
  • Retinal Cone Photoreceptor Cells / pathology
  • Retinol-Binding Proteins / deficiency
  • Retinol-Binding Proteins / genetics*
  • S Phase / physiology

Substances

  • Eye Proteins
  • Retinol-Binding Proteins
  • interstitial retinol-binding protein