Exaggerated Eye Growth in IRBP-Deficient Mice in Early Development

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. (Invest Ophthalmol Vis Sci. 2011;52:5804-5811) DOI: 10.1167/iovs.10-7129