Ophthalmology Update - Cleveland Clinic

i n v e s t i g a t i O n s
For more information, contact
George Hoppe, M.D., Ph.D.,
at hoppeg@ccf.org.
Studies on Redox-Sensitive Retinal Proteins
Continued from page 7
recently, in a rodent study, drs. hoppe and sears
found that the expression of hmgB1 in retinal photoreceptor
cells is under circadian regulation.
“Our studies show that the expression of this protein
peaks during the middle of the day and is lowest at
night, even in animals that are kept in the dark.
hmgB1 is also found in other cells, but its expression
and activity in those cells is constant rather than
cyclical,” dr. hoppe says.
Based on those findings, drs. hoppe and sears are
postulating that hmgB1 is essential for transcription
activity in the photoreceptors during daylight
hours and that it regulates or facilitates expression
of genes that are important for photoreceptor
function during the light phase.
References
chai y-c, hoppe g, and sears Je. reversal of protein
s-glutathiolation by glutaredoxin in the retinal pigment
epithelium. exp eye res 76:155-159, 2003.
hoppe g, chai y-c, and sears Je. endogenous Oxidoreductase
expression is induced by aminoglycosides.
arch Biochem Biophys 414:19-23, 2003.
Other studies with hmgB1 have led to the identification
of the function of each of its three cysteine
residues. two have been found to participate in the
formation of the intermolecular disulfide bridge that
results in altered molecular conformation and the
third is involved in mediating hmgB1 transfer in
and out of the nucleus. Upon obliteration of that
third cysteine, nucleocytoplasmic shuttling of
hmgB1 no longer occurs.
“Understanding of the regulation of transcription in
retinal photoreceptors is of interest as it may suggest
strategies for regenerating photoreceptors that are
being lost as a result of age or disease. Our finding
that the expression of hmgB1 is under circadian
control may suggest new concepts on its function,”
dr. sears says.
epithelium converts heat shock protein 70 to an
active chaperone. exp eye res 78:1085-1092, 2004.
yokoyama t, yamane K, minamoto a, mishima hK,
yamashita h, hoppe g, and sears J. protein expression
patterns of cultured human rpe cells Under
hyperglycaemic condition investigated by proteome
analysis. (in press)
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