Age-related distribution of cones and ON-bipolar cells in the rd mouse retina

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Abstract
Purpose. Retinal dystrophic (rd) mice lose most of their rod photoreceptors within the first three weeks after birth. We determined the age-related distribution of peanut agglutinin lectin (PNA)-labeled cones during the first 12 months of age. We also investigated whether the density of ON-bipolar cells expressing L7 protein was affected by their loss of photoreceptor inputs. Methods. rd mice were selected from a transgenic strain which expresses an L7-ß-galactosidase fusion gene localized to ON-bipolar cells. Cones were stained with PNA and ON-bipolar cells with bluogal (halogenated indolyl-ß-D-galactoside). Retinas were flat-mounted and observed at 1, 2, 3, 6, and 12 months of age. Results. PNA-labeled cones are distributed unevenly across the retina at 1 month postnatal. Their concentration decreases first in the central and far peripheral retina, leaving a ring of labeled cells in the midperipheral region. At 3 months, a larger patch of cones remains in the supero-temporal midperipheral region and a smaller patch in the infero-nasal retina. By 6 months, few cones remain in the infero-nasal retina; by 1 year approximately 100 cones remain in the entire retina, localized to the superior midperipheral region. ON-bipolar cells appear evenly distributed at 1 month. By 2–3 months, relatively more bluo-gal staining is seen in the midperipheral regions underlying dense cone populations. At 6–12 months, bluo-gal label is distributed in a spotty pattern with little or no staining seen in areas of apparent neovascularization. Conclusions. (1) PNA-labeling of cones in the rd retina deteriorates in a distinct spatial pattern with the longest cone survival in the midperipheral superior retina. (2) ON-bipolar cells are more densely labeled in regions of high cone density during the early months of cone degeneration and, in later stages, show relative decreases in regions of apparent neovascularization.