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John S. Penn, Shihong Li, Muna I. Naash; Ambient Hypoxia Reverses Retinal Vascular Attenuation in a Transgenic Mouse Model of Autosomal Dominant Retinitis Pigmentosa. Invest. Ophthalmol. Vis. Sci. 2000;41(12):4007-4013.
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purpose. Loss of retinal capillaries is an inherent component of late stage
autosomal dominant retinitis pigmentosa (ADRP). This study examined the
hypothetical role of tissue hyperoxia in this vascular attenuation
process and tested the potential of ambient hypoxia to reverse it.
methods. Transgenic mice expressing a mutant opsin gene with a 3-bp deletion of
isoleucine at codon 255/256 were used. This model is characterized by
early onset of a rapidly progressing retinal degeneration that by
postnatal day (P)20 results in the loss of all but one row of
photoreceptor nuclei. At P20 some mice were placed in 12% oxygen until
they were euthanatized at P26. The remainder were maintained in
normoxia and killed at the same age. Retinas were dissected, stained
for ADPase, and flat-mounted.
results. Deep plexus capillary density was significantly different in normoxic
normals versus transgenics at 20 days of age (P ≤
0.005). An additional 65% reduction of capillary density occurred
within the deep plexus of normoxic transgenics between P20 and P26
(P ≤ 0.005). Ambient hypoxia between days P20 and P26
reversed this trend, causing an increase in deep capillary
plexus density of nearly 100% (P ≤ 0.001).
conclusions. This model of ADRP demonstrates two important features of human
retinitis pigmentosa: photoreceptor cell death and subsequent retinal
capillary atrophy. Low ambient oxygen was used to reverse the capillary
atrophy and to stimulate new capillary growth, implying that retinal
oxygen tension may link these two features of the pathology. The
implications of this study hold importance for strategies designed to
treat retinitis pigmentosa with retinal cell
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