Tiger salamanders have been used in visual science because of the larg
e size of their cells and the ease of preparation and maintenance of i
n vitro retinal preparations. We have found that salamanders over 27 c
m in length show a variety of visual abnormalities. Compared to smalle
r animals (15-23 cm), large animals exhibited a decrease in visual res
ponses determined by tests of the optomotor reflex. Small animals resp
onded correctly an average of 84.5% of the time in visual testing at t
hree light levels compared to an average of 68.4% for the large animal
s with the poorest visual performance at the lowest level of illuminat
ion. In addition, large animals contained (i) histological degeneratio
n of the outer retina, in particular, loss and disruption of outer seg
ments and abnormalities of the retinal pigmented epithelium, (ii) loss
of cells, including photoreceptors, by apoptosis as evaluated with th
e TUNEL technique, and (iii) an increase in the number of macrophages
and lymphocytes within the retina as determined by morphological exami
nation. These histological changes were present in all large animals a
nd all quadrants of their retinas. In contrast, small animals showed v
irtually no retinal degeneration, no TUNEL-positive cells, and few imm
une-like cells in the retina. Since large animals are also older anima
ls, the visual changes are age-related. Loss of visual function and hi
stological degeneration in the outer retina also typify aged human eye
s. Thus, we propose that large salamanders serve as an animal model fo
r age-related retinal degeneration. In addition to providing a source
of aging retina that is readily accessible to experimental manipulatio
n, the salamander provides a pigmented retina with a mixed (2:1, rod:c
one) population of photoreceptors, similar to the degeneration-prone p
arafoveal region of the human eye. (C) 1998 Academic Press Limited.