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A $65,000 grant was awarded to Sriganesh Ramachandra Rao, Ph.D., who is a Postdoctoral
Associate at State University of New York, Buffalo, VA Western New York Healthcare System.
This grant aims to further understand the role of the gene DHDDS during retinal development.

Making the check presentation were Sir Knights from the Grand Commandery of New York: David D.
Goodwin, Past Grand Master of the Grand Encampment and Past President and Trustee of the Knights
Templar Eye Foundation; David Hardy, Grand Commander; Steven Wing, Past Grand Commander and
Grand Recorder; W. Bruce Renner, Past Commander; and Aide-de-camp to PGM Goodwin; present with
Dr Rao was Steven Fliesler, Ph.D, Preceptor, and Vice Chair & Director of Research

Autosomal recessive Retinitis Pigmentosa-59 (arRP59) — an early-onset, progressive and
irreversible hereditary blinding disorder— involves degeneration of photoreceptor (PR) cells,
for reasons that remain unclear. The disease is caused by mutations in the gene encoding
DHDDS (dehydrodolichyldiphosphate synthase), an enzyme required for the synthesis of a
lipid molecule (dolichol) essential for adding sugars to proteins (N-glycosylation) in cells.
However, contrary to expectations, cells from patients carrying known DHDDS mutations
surprisingly lack any obvious glycosylation defects.
To understand the mechanism underlying this disease requires generation of novel genetic
animal models that faithfully mimic DHDDS dysfunction and, hence, cause dolichol
synthesis defects. They recently generated the first viable vertebrate model of arRP-59, by
genetically ablating the Dhdds gene selectively in just the retinal rod PR cells in mice, but
at a time point after PR cell fate had been specified. This animal model exhibits rapid PR
degeneration, but curiously without obvious protein glycosylation defects.
Several studies suggest a requirement for dolichol synthesis
during cell fate determination, cell cycle progression and
tissue development. Hence, they hypothesize that if DHDDS
is ablated prior to differentiation of PR cells, disruption of
normal retinal development will occur, resulting in blindness.
The proposed project aims to further our understanding of
the role of Dhdds during retinal development, with relevance
to the retinal dysfunction and degeneration observed in arRP-
59 patients with “severe” DHDDS mutations. The proposed
study will advance our fundamental understanding of dolichol
homeostasis and N-glycosylation during photoreceptor
genesis, as well as disease mechanisms pertaining to this
pediatric blinding disorder.

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