Linda L. Collier

Ocular melanin pigmentation anomalies in cats, cattle, mink, and mice with Chediak-Higashi syndrome: Histologic observations

The Chediak-Higashi syndrome (CHS) is a hereditary disorder of man, with the homologous condition reported in five animal species. Multiple defects, including oculocutaneous hypopigmentation, are present in individuals with this syndrome. Giant cytoplasmic granules, including melanosomes and lysosomes, are characteristic. In this study, eyes from CHS affected and control cats, cattle, mink, and mice were examined histologically to determine: 1) degree of pigmentation; 2) structure and distribution of melanin granules; and 3) morphology of cells and tissues containing melanin. The CHS cattle were found to be the most ocularly hypopigmented species, whereas CHS mouse eyes contained considerably more melanin than those of the other species. Melanin granules of abnormal sizes and shapes were present in neuroepithelial and uveal tissues of CHS animals of all four species. Depigmentation apparently had occurred in the CHS eyes, since less melanin was present in eyes of old CHS animals of each species than was present in eyes of young animals. In addition, melanin containing macrophages were common in CHS eyes, and the numbers of melanocytes and pigmented epithelial cells were decreased in older CHS eyes.

Aberrant melanosome development in the retinal pigmented epithelium of cats with Chediak-Higashi syndrome

The Chediak-Higashi syndrome is a genetic disorder characterized by greatly enlarged cytoplasmic granules, including lysosomes and melanosomes. Eyes of humans and animals with Chediak-Higashi syndrome are hypopigmented to various degrees. Intraocular melanin granules vary in size, with some being massively enlarged. Electron microscopic examination of retinal pigmented epithelium of kittens with Chediak-Higashi syndrome disclosed a number of abnormalities of premelanosomes and melanosomes. Few premelanosomes were present. Most of the melanin granules were giant sized, but their structures varied. Some of the giant granules were composed of several premelanosomes and melanosomes in different stages of maturation. Others contained randomly oriented melanofilaments between melanosomes. There were also complex giant granules consisting of both melanosomal and lysosomal components. Inappropriate fusion of cytoplasmic granules appears to be the most likely mechanism for formation of the giant granules. Fusion of premelanosomes with lysosomes and resultant destruction of the premelanosomes probably is a major cause of the ocular hypopigmentation of Chediak-Higashi syndrome.

Tapetal degeneration in cats with Chediak-Higashi syndrome

The Chediak-Higashi syndrome (CHS) is a genetic disorder of man, cats, and four other animal species. Enlarged cytoplasmic granules, including lysosomes and melanosomes, characterize the syndrome. Cats affected with CHS lack funduscopically visible tapeta. In normal cats, the tapetum is the light reflecting cellular layer located in the choroid. The tapetal cells contain bundles of parallel cytoplasmic rods. In this study, eyes from CHS and control cats were examined by light microscopy and transmission electron microscopy. The CHS kittens up to 14 days of age had tapeta which appeared similar to those of the controls. By 28 days of age some of the CHS tapetal rods had degenerated. Degeneration of the tapetal rods progressed rapidly and by 56 days of age there was a dramatic difference in the ultrastructural appearance of the tapetal cells. All the rods had degenerated and the contents of the tapetal cells were disorganized. The tapetal layer gradually thinned over a period of several months until the layer was absent or nearly so in CHS cats over one year of age. This study demonstrated that there is a previously overlooked degenerative component of the Chediak-Higashi syndrome.

Auditory Brainstem Responses in Cats with Chediak-Higashi Syndrome

Auditory brainstem responses ABRs were recorded in cats with Chediak-Higashi syndrome using monaural stimulation. The components appearing between 1 and 3 ms after stimulus onset were greatly attenuated in the ABRs recorded using a reference contralateral to the stimulated ear. These data suggest that abnormalities exist in the brainstem auditory pathway in the region of the superior olivary complex in cats with Chediak-Higashi syndrome.