Elsevier. BRE 10763. Retinal Ganglion Cell Loss Produced by Intraocular Kainic Acid in Cats: Variation with Somal Size and Eccentricity. LEONARD J. TREJO.
Brain Research, 335 (1985) 221-230
221
Elsevier BRE 10763
Retinal Ganglion Cell Loss Produced by Intraocular Kainic Acid in Cats: Variation with Somal Size and Eccentricity LEONARD J. TREJO
Department of Ophthalmology, RJ-IO, University of Washington School of Medicine, Seattle, WA 98195 (U, S. A. ) (Accepted August 28th, 1984)
Key words: kainic acid - - neurotoxicity - - cat - - retinal ganglion cells - - somal size - - eccentricity
Eight eyes of adult cats were injected with different doses of kainic acid (KA) and examined following survival times of either 5 or 12 days. At a survival time of 12 days, a dose of 76 nmol produced an 18% loss of ganglion cells in the center of the area centralis (AC), 70% loss at a location 2 mm from the AC, and 95% loss at a location 6 mm from the AC. Larger doses (240,760 and 2400 nmol) produced losses comparable to that observed for 76 nmol. For example, 2400 nmol produced a 35% loss in the AC, 81% at 2 mm, and 88% at 6 ram. At a survival time of 5 days, doses of 240 and 760 nmol produced a loss of ganglion cells comparable to that seen at 12 days. In one eye, a large dose of KA (7600 nmol) produced total loss of ganglion cells at a survival time of 5 days. By comparing loss of cells in restricted somal diameter ranges at different retinal eccentricities, it was possible to distinguish two significant correlations that were largely independent of survival time and dose: (1) at 2 ram, loss of cells with somal diameters larger than 21 ,um significantly exceeded loss of cells with smaller somata. In particular, alpha cells were totally eliminated in 6 of the 8 KA-treated eyes. (2) The mean loss ol ganglion cells with somal diameters less than 21/~m was significantly greater at 2 mm and 6 mm than in the AC. Together. these results show that loss of ganglion cells produced by KA varies somal size and retinal eccentricity.
INTRODUCTION
of K A , r e l a t i v e to cells of o t h e r classes, a p p e a r s to vary b e t w e e n species. A low sensitivity is r e p o r t e d
Kainic acid ( K A ) is a structural a n a l o g of g l u t a m i c
for the chicken 11, m o d e r a t e sensitivity in the cow and
acid that has specific p h y s i o l o g i c a l effects on retinal
goldfishS,31 and a high sensitivity in the rat 6,7, rabbit
n e u r o n s . In the m u d p u p p y r e t i n a , S l a u g h t e r and Mil-
and human8.
ler21-23 h a v e s h o w n that K A is p r o b a b l y an a n a l o g of p h o t o r e c e p t o r and b i p o l a r cell t r a n s m i t t e r s .
Partial loss is k n o w n to o c c u r within single classes of retinal n e u r o n s . F o r e x a m p l e , a f r a c t i o n of gangli-
K A is also a n e u r o t o x i n and is k n o w n to p r o d u c e
on cells survives after i n t r a o c u l a r i n j e c t i o n of K A in
n e u r o n a l loss with v a r y i n g d e g r e e s of specificity in the retina3,6-s,to~11,14, 31 and t h e brain2, 5,t6,17,29. In ver-
the eyes of chickens 11, rats 6 and cats 2°. This suggests
t e b r a t e retinas, e v e r y m a j o r class of cells ( e . g . am-
cells that resist K A are distinct f r o m t h o s e that are
the possibility, not yet i n v e s t i g a t e d , that the g a n g l i o n
acrine, bipolar, g a n g l i o n , etc.) c o n t a i n s e l e m e n t s
susceptible to it in t e r m s of t h e i r m o r p h o l o g y and
that are e l i m i n a t e d by i n t r a o c u l a r K A ; h o w e v e r , the
physiology, o r in t e r m s of o t h e r p r o p e r t i e s such as the
n e u r o n s of the i n n e r n u c l e a r layer are the m o s t sensi-
n a t u r e of their a f f e r e n t input and their position in the
tive 19. F o r e x a m p l e , in the c h i c k e n retina, 2 m M K A
retina.
eliminates m o s t of the b i p o l a r and a m a c r i n e cells in
T h e aim of this study was to test for d i f f e r e n c e s be-
the inner n u c l e a r layer l~. Successively larger doses
t w e e n ganglion cells that resist K A and t h o s e that are e l i m i n a t e d by K A in the cat retina. T h e cat retina was
are r e q u i r e d to e l i m i n a t e h o r i z o n t a l cells, g a n g l i o n cells, and p h o t o r e c e p t o r s . T h e sensitivity of g a n g l i o n cells to the toxic effects
chosen b e c a u s e the spatial density of g a n g l i o n cells of a given somal
size
at
different
eccentricities
is
Correspondence: L. J. Trejo. Present address: Neuroscience Group, Navy Personnel Research and Development Center, San Diego. CA 92152, U.S.A. 0006-8993/85/$03.30 © 1985 Elsevier Science Publishers B.V. (Biomedical Division)
222 known 9.27 and at a given retinal eccentricity, there is some correlation between somal size and cell type 1,26. In particular, the alpha type is easily distinguished from other types throughout the retina by virtue of its very large somal size 30. Thus, by comparing the somal size distribution of surviving ganglion cells at selected eccentricities in a KA-treated eye and an untreated eye, it is possible to determine whether the toxic effects of KA vary with somal size or eccentricity. A preliminary account of the results of this study has been presented 28. MATERIALS AND METHODS
segments of the eyes were subsequently postfixed tot 18-24 h. The retinas were dissected free ira cold phosphate buffer (pH 7.4) and mounted flat on gelatinized slides. Care was taken to minimize shrinkage by exposure of the freshly mounted retinas to formaldehyde vapors 25 in a closed container for about 12 h at room temperature. The retinas were then soaked in a 3% mixture of acetic acid in ethanol for 30 mm
