Studies on the visual system of the rat

Minimal structural changes, not detected by qualitative assessment require quantitative methods for recognition. This work is concerned with the development of such a quantitative technique, and its application to minimal change situations, namely the visual cortices of rats with retinal dystrophy (Campbell strain) and of rats which had received a low grade retinotoxic insult.

As well as the anatomy and normal development, the literature survey included those factors which can influence the normal development and function of the visual system, and hence the quantitative data. The quantitation review demonstrated the diversity of approach of the various authors working in this field, and revealed how little quantitative data exists on the rat cerebrum. No reports could be found on visual system quantitation of either of the situations investigated in this work.

In the section on the problems of quantitation, the high technical demands and inherent errors are discussed, and the methods and correction factors to overcome these problems are detailed. Strict comparability of sections was attained by devising a method which ensured similar anatomical location in every case, despite great variation in brain size.

A technique was devised to measure the variable shrinkage of processing, a problem ignored by many authors. By means of this Reduction Factor, the exact volume of tissue in a section is known and quantitative data can be calculated in a standard comparable form.

From a total of 1,500 sections, after screening by ophthalmoscopy, post mortem examination, section thickness control and histological scrutiny, some 950 sections were selected for quantitation. The 950 sections, from 190 individuals provided the large sample, necessary because of individual variation.

The quantitative results are presented in graphical and statistical forms, subdivided by age, sex and strain. These results show the method revealed differences between the dystrophic (Campbell) and control (P.V.G.) visual cortices. The Campbell cortex has a smaller mean cell size, which is produced by two factors, namely an increase in small cell density and a decrease in the density of the largest cells. Ultrastructural and special light microscopic investigation identified these cells as microglia and neurones respectively.

These results, which have never previously been reported in the rat compare well with those produced in other species with visual deprivation and are consistent with the results of biochemical investigation of the Campbell visual cortex.

The retinotoxic drugs, two diaminophenoxy compounds and iodoacetate which are retinotoxic in other species at the dose schedule used, failed to cause any changes in the P.V.G. rat by ophthalmoscopic, histological or quantitative investigation. It would seem the rat eye is relatively resistant to such drugs, and it is suggested that species other than the rat should be used to determine retinotoxicity.