Meredithe
L. Applebury, Ph.D
Professor
of Ophthalmology
Massachusetts Eye & Ear Infirmary
Howe Laboratory
243 Charles Street
Boston, MA 02114
Tel.: (617) 573-4373
Fax.: (617) 573-3751
Our laboratory
is pursuing three areas of investigation: (1) We have actively
explored the molecular basis of primary visual signaling
for many years. Current studies examine the structure, function,
and regulation of guanylate cyclase which controls the levels
of cGMP messenger in rods and cones. Our attention has turned
to defining the molecular mechanisms by which cones signal. Signaling
components, cloned from mammalian cones, are expressed in vitro
in host mammalian cells using a vaccinia vector system and isolated
for mechanistic study. We seek to characterize the molecular properties
that distinguish cone signaling and adaptation from that of rods.
(2) We have used marker genes to map the spatio-temporal development
and organization of rods and cones in the murine retina. Blue
cones differentiate before rods. They are followed by the appearance
of red/green cones. We have introduced genes into transgenic mice
to ablate each cell type. The studies are designed to examine
how each cell provides the correct environment to induce differentiation
of other photoreceptor cell types, and to maintain an environment
in which neighboring rods and cones survive. (3) We and others
have identified the defective gene that causes retinal degeneration
in the rd mouse to be the b -subunit of cGMP phosphodiesterase
(PDE). The gene has been altered by insertion of a retrovirus
and codon mutations that result in product truncation. Studies
now address how these gene defects affect the expression of the
PDE in rods, in other retinal and CNS cells, and how these defects
lead to cell death. Trainees might choose an aspect of any of
these projects for research.
Research 
Publications
Lab Members Links
Howe
Home Page 
E-Mail: mapplebury@meei.harvard.edu