Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leber congenital amaurosis (LCA) caused by mutations in Aryl hydrocarbon receptor interacting protein like-1 (Aipl1) is a severe form of childhood blindness. At 4 weeks of age, a mouse model of LCA lacking AIPL1 exhibits complete degeneration of both rod and cone photoreceptors. Rod cell death occurs due to rapid destabilization of rod phosphodiesterase, an enzyme essential for rod survival and function. However, little is understood regarding the role of AIPL1 in cone photoreceptors. Cone degeneration observed in the absence of AIPL1 could be due to an indirect 'bystander effect' caused by rod photoreceptor death or a direct role for AIPL1 in cones. To understand the importance of AIPL1 in cone photoreceptor cells, we transgenically expressed hAIPL1 exclusively in the rod photoreceptors of the Aipl1(-/-) mouse. Transgenic expression of hAIPL1 restored rod morphology and the rod-derived electroretinogram response, but cone photoreceptors were non-functional in the absence of AIPL1. In addition, the cone photoreceptors degenerate, but at a slower rate compared with Aipl1(-/-) mice. This degeneration is linked to the highly reduced levels of cone PDE6 observed in the hAIPL1 transgenic mice. Our studies demonstrate that AIPL1 is needed for the proper functioning and survival of cone photoreceptors. However, rod photoreceptors also provide support that partially preserves cone photoreceptors from rapid death in the absence of AIPL1.
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PMID:The Leber congenital amaurosis protein, AIPL1, is needed for the viability and functioning of cone photoreceptor cells. 2004 64

Mutations in Aryl hydrocarbon receptor interacting protein like-1 (AIPL1) are linked to Leber congenital amaurosis (LCA), a severe blinding disease that occurs in early childhood. The severity of disease is due to requirement for AIPL1 in both rod and cone photoreceptor cell survival and function. Aipl1 is expressed very early during retinal development in both rods and cones. In adult primates, robust expression of Aipl1 is found in rods but not in cones. Mouse models revealed the importance of AIPL1 in stability and function of heteromeric phosphodiesterase 6 (PDE6), an enzyme needed for visual response. However, the need for AIPL1 in cone cell survival and function is not clearly understood. In this chapter, using results obtained from multiple lines of animal models, we discuss the role for AIPL1 in photoreceptors.
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PMID:AIPL1 protein and its indispensable role in cone photoreceptor function and survival. 2466 79