One day last summer, a 62-year-old man suffered sudden,drastically reduced visual acuity. He experienced fuzzycentral vision and a diminished sense of brightness inboth eyes.
Ophthalmological examination revealed loss of colorsense and peripheral vision, plus severe dysfunction ofthe rod and cone cells in his retinas. A routine physicalfound no history or current indication of cancer.
His unexplained, progressive slide toward blindness gavethe specialists concern that he might be suffering from acancer-related eye disease. One of the pathologies theysuspected is Lambert-Eaton syndrome, which afflictspatients with carcinoma.
It's caused by autoantibodies against motor-neuron axonterminals. That is, by an autoimmune disease.
In similar cases, the chief of ophthalmology at theUniversity of California Davis Medical Center, JohnKeltner, had prescribed an immune suppressor drug,prednisone. It stabilized this patient's alarminglydeclining vision.
His condition, presumed akin to Lambert-Eaton, alsosuggested another unusual syndrome, cancer-associatedretinopathy (CAR). This implies that an aberrant antigengives rise to antibodies in a neoplastic tumor that migrateto a distant site in the nervous system, and there producesa similar aberration.
The human retina harbors a protein for suchautoantibodies, inaptly dubbed "recoverin" for irrelevanthistorical reasons. This is a 26 kD peptide that normallyresides in the retinal photoreceptor cells of each eye,namely the 130 million cylindrical rods, and the sevenmillion pyramid-shaped cones.
Rhodopsin, a.k.a. visual purple, inhabits the retinal rodcells, where light rays bleach its red substance, andconvert it to opsin. Hence, this high-dose of visual purpleresponds to low levels of illumination, and equips therods for night vision.
On the other hand, the far fewer cones accommodate asmaller supply of a paler pigment, iodopsin, or visualviolet, which resolves images with high acuity bydaylight.
The recoverin molecule's function in retinal rods andcones is unknown, but its connection to pulmonary, andperhaps gynecological, cancers is more than stronglysuspected. Sure enough, that blurred-vision patient turnedout to have a small, small-cell carcinoma in his rightlung.
And that tumor contained anti-recoverin antibodies, along way from their home base in the retina. Moreover,his retinal photoreceptors and blood contained suchantibodies too. But other lung-cancer patients, with noparaneoplastic echo in the retina, showed no trace ofrecoverin in their tumors or serum.
A paper in the current Proceedings of the NationalAcademy of Sciences (PNAS), dated Sept. 26, 1995,brings this story up to date. Its title: "Recoverin, aphotoreceptor-specific calcium-binding protein, isexpressed by the tumor of a patient with cancer-associated retinopathy [CAR]."
Its first author is biochemist Arthur Polans, who movesnext week from the Dow Neurological Sciences Instituteat Legacy-Good Samaritan Hospital in Portland, Ore. tothe University of Wisconsin's ophthalmology andbiomolecular chemistry department in Madison.
Polans told BioWorld Today that his PNAS paper"reports for the first time that recoverin is indeedexpressed in distant tumors."
He explained that "recoverin is found normally only inretinal and pineal-gland photoreceptors, which aresequestered from the immune system. It belongs to aprotein family, of which calmodulin is the best-knownmember, involved in the transduction of light byvertebrate receptors."
Recoverin's diagnostic and prognostic potential did notescape Polans' notice. He is first inventor of U.S. patentnumber 5,405,749, dated April 11, 1985, and assigned tothe Dow Institute. It is headed: "Method for identifyingand purifying a cancer associated retinopathy autoantigen,and testing patient serum for the autoantibody to theautoantigen." n
-- David N. Leff Science Editor
(c) 1997 American Health Consultants. All rights reserved.