M. Carter Cornwall, PhD

Professor of Physiology and Biophysics

B.S. University of Utah
Ph.D. University of Utah

Phone: (617) 638-4256
Fax: (617) 638-4273
e-mail: cornwall@bu.edu
address: see below

Research

Dark Adaptation in Vertebrate Photoreceptors

The work in our laboratory is focused on understanding the response
of the vertebrate eye to and recovery from the effects of bright light.
Our principal approach is to make electrophysiological measurements of
rod and cone photoreceptors of cold-blooded vertebrate animals, and to
correlate these physiological responses to microspectrophotomeric
measurements of the visual pigments as well as microfluorometric
measurements of the concentration of vitamin A and Ca2+ contained within
the cells. The reduction of all–trans retinal to Vitamin A is one of
the principal initial steps that must occur following exposure to bright
light to allow recovery of sensitivity (dark adaptation). Experiments
have also shown that Ca2+ is a principal messenger substance during
bright (bleaching) adaptation.

The Visual Cycle

Bleaching of rhodopsin (Rh) produces a photoactivated methrhodopsin
II (R*), which decays through a series of intermediates to opsin and
all-trans retinal. All-trans retinal is reduced within the photoreceptor
to all-trans retinol, which is then transported via the
interphotoreceptor retinol binding protein (IRBP) through the
extracellular space to an adjacent layer of epithelial cells, called the
retinal pigment epithelium (RPE). Within the RPE, the all-trans retinal
is bound to cellular retinol binding protein (not shown) and then is
esterified to fatty acits, mostly palmitic acid. The ester is converted
by retinoid isomerase to 11-cis retinol, which is bound to yet another
binding protein and oxidized by oxidoreductase to 11-cis retinal.
Interphotoreceptor binding protein then returns the 11-cis retinal to
the photreceptor, where it recombines with opsin to form dark adapted
Rh.

Retinol Fluorescence

Our most recent work has focused on the time course of changes in
retinol fluorescence intensity following a large bleach of the visual
pigment. The bright field image at top left shows cellular fragments as
well as one intact cone (lower left) and one intact red rod (upper
right). The cells were suspended in a bath that had been mounted on the
stage of the fluorescence microscope. The second field on the top row
shows a fluorescence image obtained before visual pigment bleaching (T =
0.00 min). It is apparent that both intact cells exhibit a large amount
of fluorescence in their ellipsoid regions. This fluorescence is
consistent with the large concentration of mitochondria located there,
and likely results from the high concentration of NADH in mitochondria.
The cell was then exposed to sufficient bright green (500 nm) light to
bleach in excess of 99% of the visual pigment contained in the outer
segments of both cells. The top right panel (T = 0.52 min.) shows a
large uniform increase in fluorescence in the region of the cone outer
segment, and a small amount of fluorescence beginning to appear in the
most proximal part of the outer segment of the rod. The bottom panel on
the left (T = 13.09 min.) shows that by this time, much of the outer
segment fluorescence in the cone had dissipated; however, the
fluorescence in the rod outer segment continued to increase, and
appeared to uniformly fill the outer segment of the rod. The image in
the second panel from the left, bottom row (T = 37.80 min.) shows that
the fluorescence in the cone outer segment by this time was very low,
but that in the outer segment of the rod had achieved a maximum level.
At this time 2 :m bovine IRBP was added to the bath. Thereafter, the
fluorescence in the rod outer segment was observed to decline. The last
measurement of fluorescence was made 87.82 min following the initial
pigment bleach.

Publications

Cornwall, M.C. and G.L. Fain (1994) Bleached
pigment activates transduction in isolated rods of the salamander
retina. J. Physiol. 480: 261-279.

Cornwall, M.C., H.R. Matthews, R.K. Crouch and
G.L. Fain. (1995) Bleached pigment activates phototransduction in
salamander cones. J. Gen. Physiol. 106: 543-557.

Matthews, H.R., G.L. Fain, and M.C. Cornwall.
(1995) Role of cytoplasmic calcium concentration in the bleaching
adaptation of salamander cone photoreceptors. J. Physiol. 490: 293-303.

Matthews, H.R., M.C. Cornwall, and G.L. Fain.
(1996) Persistent activation of transducin by bleached rhodopsin in
retinal rods. J. Gen Physiol. 108:557-563.

Matthews, H.R., G.L. Fain, and M.C. Cornwall
(1996) Role of cytoplasmic calcium concentration in the bleaching
adaptation of salamander cone photoreceptors. J. Physiol. 490:293-303.

Fain, G.L., H.R. Matthews, and M. C. Cornwall. (1996) Dark adaptation in vertebrate photoreceptors. TINS 19:502-507.

Sampath, A.P., H.R. Matthews, M. C. Cornwall, J.
Bandarchi, and G.L. Fain. (1999) Light-dependent changes in outer
segment free-Ca2+ concentration in salamander cone photoreceptors. J.
Gen Physiol. 113:1-11.

Kefalov, V.J., M. C. Cornwall, and R.K. Crouch
(1999) Occupancy of the chromophore binding site of opsin activates
visual transduction in rod photoreceptors. J. Gen. Physiol. 113:491-503.

Contact Us

Department of Physiology and Biophysics
Boston University Chobanian & Avedisian School of Medicine
72 East Concord Street
Boston MA 02118-2526

Phone: (617) 638-4256
Fax: (617) 638-4273
e-mail: cornwall@bu.edu