Dose-response analysis of effects of antibodies to large ganglion cells on the cat's retinogeniculate pathways

Abstract

Previous studies have shown that antibodies against large retinal ganglion cells (alpha-/Y-cells) reduce the Y-cell retinogeniculate pathway while having little or no effect on the X- or W-cell pathways. The present study investigated the dose-response relationship of these effects. We began by studying effects on the T1 (largely Y-cell-mediated) and T2 (largely X-cell-mediated) waves of the retinal field-potential. Different concentrations of the antibodies were injected intraocularly in adult cats and retinal field-potentials evoked by optic chiasm stimulation were examined. The lowest concentration of immune serum tested (330 micrograms/100 microliter volume) reduced both the T1 and T2 amplitudes. With increasing concentrations, the ratio of T1:T2 amplitudes progressively decreased from 0.71 to only 0.05. The highest concentration of immune serum tested (1000 micrograms/100 microliter volume) virtually eliminated the T1 wave while the T2 wave remained (albeit reduced). Next, we carried out single-cell physiological and morphological studies to verify the effects of the highest antibody concentration and compare them with previous results on effects of the lowest antibody concentration (Kornguth et al., 1982; Spear et al., 1982). In single-cell recordings from the retina, the encounter rates of Y- and X-cells were reduced by 85 and 53%, respectively, after injection of the highest antibody concentration. There was no effect on the encounter rate of retinal W-cells. After injection of the lowest antibody concentration, there was no change in the encounter rates of any of the retinal cell types. Morphological studies revealed an 88-99% loss of alpha-cells in retinae treated with the highest antibody concentration. There also was a substantial (24-57%) loss of medium-size ganglion cells but no loss of small ganglion cells. The loss of alpha-cells was much greater after high-concentration injections than after low-concentration injections. In recordings from the LGN, the proportion of Y-cells was reduced by 87% in laminae receiving input from an eye injected with the highest antibody concentration. Laminae receiving input from an eye injected with the lowest concentration had a 77% reduction in Y-cells. The encounter rate of LGN X-cells was not affected by either concentration. Morphological analysis indicated that the loss of Y-cells in the LGN was not due to changes in cell size. These findings indicate that antibody-mediated effects on retinogeniculate pathways are dose-dependent.(ABSTRACT TRUNCATED AT 400 WORDS)

Responses of lateral geniculate neurons that survive long-term visual cortex damage in kittens and adult cats

“…Even though we avoided some commonly used criteria for classifying cells, our results in normal cats were similar to those reported elsewhere. Layers A and Al contained almost exclusively X and Y cells, and the percentages were similar to those found in other studies (e.g., Hoffmann et al, 1972;Cleland et al, 1976;Wilson et al, 1976;Friedlander and Stanford, 1984;Crabtree et al, 1986;McCall et al, 1987). A few cells were classified as W in the normal A-layers, which is somewhat atypical.…”

“…Because the properties of A-layer cells vary somewhat with depth in the layer (Mitzdorf and Singer, 1977;Wieniawa-Narkiewicz, 1986, 1987), these samples may not be sufficiently random to be representative of A-layer cells in normal cats. However, both the qualitative and quantitative results for normal A-layer cells in our sample are similar to those of other studies in which the A-layer sampling was more complete (e.g., Derrington and Fuchs, 1979;So and Shapley, 1979;Lehmkuhle et al, 1980;Troy, 1983;Crabtree et al, 1986;McCall et al, 1987). Therefore, our A-layer sample does seem to be representative.…”

“…Figure 6 shows the percentages of cells classified as X, Y, W, or UC in the A-and C-layers of each group of cats. In the A-layers of normal cats, 62% of the cells encountered were classified as X cells and 28% were classified as Y cells, percentages that agree with previous reports (e.g., Hoffmann et al, 1972;Cleland et al, 1976;Wilson et al, 1976;Friedlander and Stanford, 1984;Crabtree et al, 1986;McCall et al, 1987). About 10% of the cells were classified as W cells or UC.…”

“…Animal preparation. Each cat was prepared for single-cell recordings in the LGN using standard procedures Crabtree et al, 1986). During all surgery, the cat was anesthetized with halothane in 50% 0,/50% N,O.…”

A Proposed Mechanism for Development of CTE Following Concussive Events: Head Impact, Water Hammer Injury, Neurofilament Release, and Autoimmune Processes

“…These antibodies to the NF proteins reacted with the small cell cancer as well as the large retinal ganglion cells affected by the visual paraneoplasia. The anti-neurofilament antibodies resulted in the selective immunoablation of large retinal ganglion cells following injection of these antibodies into cat vitreous [ 29 , 30 ]. These observations on the SCCL population are supportive of the observation by Shahim [ 14 , 15 ] that the l NF proteins seen in the mild TBI (mTBI) pass from the neuronal compartment into the cerebrospinal fluid (CSF) over a prolonged time period.…”