Progress toward understanding the genetic and biochemical mechanisms of inherited photoreceptor degenerations.
More than 80 genes associated with human photoreceptor degenerations have been identified. Attention must now turn toward defining the mechanisms that lead to photoreceptor death, which occurs years to decades after the birth of the cells. Consequently, this review focuses on topics that offer insights into such mechanisms, including the one-hit or constant risk model of photoreceptor death; topological patterns of photoreceptor degeneration; mutations in ubiquitously expressed splicing factor genes associated only with photoreceptor degeneration; disorders of the retinal pigment epithelium; modifier genes; and global gene expression analysis of the retina, which will greatly increase our understanding of the downstream events that occur in response to a mutation.
Pacione
Laura R
LR
Programs in Genetics and Developmental Biology, The Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8.
Szego
Michael J
MJ
Ikeda
Sakae
S
Nishina
Patsy M
PM
McInnes
Roderick R
RR
D000818:Animals; D001671:Biochemistry / Q000379:methods; D016923:Cell Death; D004195:Disease Models, Animal; D015870:Gene Expression / Q000502:physiology; D008040:Genetic Linkage; D006801:Humans; D008967:Molecular Biology / Q000379:methods; D019636:Neurodegenerative Diseases; D010786:Photoreceptor Cells / Q000166:cytology / Q000502:physiology*; D012326:RNA Splicing / Q000235:genetics / Q000502:physiology; D012162:Retinal Degeneration / Q000145:classification / Q000235:genetics* / Q000378:metabolism*; D012174:Retinitis Pigmentosa