Ambient hypoxia reverses retinal vascular attenuation in a transgenic mouse model of autosomal dominant retinitis pigmentosa.

Penn JS, Li S, Naash MI
Invest Ophthalmol Vis Sci. 2000 41 (12): 4007-13

PMID: 11053306

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:
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 transplantation.

MeSH Terms (16)

Animals Apyrase Atrophy Capillaries Cell Death Disease Models, Animal Female Hypoxia Male Mice Mice, Inbred C57BL Mice, Transgenic Photoreceptor Cells, Vertebrate Retinal Vessels Retinitis Pigmentosa Rod Opsins

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