Guanylyl Cyclase Genes and Their Role in Retinal Degeneration

  • Hans-Jürgen Fülle
  • Rima Khankan


Guanylyl cyclases play a fundamental role in a wide variety of cellular processes. In response to specific regulatory signals these enzymes form the intracellular second messenger molecule cGMP. In vertebrate retinal photoreceptor cells cGMP has been identified as the primary internal messenger for visual transduction more than a decade ago. Inherited defects in cGMP metabolism have been linked to retinal degeneration and blindness even longer. Recently, specific gene defects in one of the retinal isoforms of guanylyl cyclase, RETGC-1, have been found to cause Leber’s congenital amaurosis (LCA) and an autosomal-dominant form of cone-rod dystrophy. We investigated the functional consequences of a RETGC-1 missense mutation (F589S) described in LCA patients. We demonstrate that this mutation markedly decreases enzyme activity when expressed in vitro. Function and possible linkage to eye disease of an X-chromosomal gene encoding a second retinal isoform, RETGC-2, are less clear. We determined the genomic structure of RETGC-2 as a prerequisite for future mutation screening studies.


Retinitis Pigmentosa Guanylate Cyclase Photoreceptor Cell Guanylyl Cyclase Retinal Degeneration 
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© Kluwer Academic / Plenum Publishers 1999

Authors and Affiliations

  1. 1.Department of Cell and NeurobiologyUniversity of Southern California School of MedicineLos Angeles

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