Lysosomes and melanin granules of the retinal pigment epithelium in a mouse model of the Chediak-Higashi syndrome.

The origin of giant granules in the retinal pigment epithelium of the beige mouse was investigated with electron microscopy and ultrastructural histochemistry. These granules were found to contain melanin and acid phosphatase. Apparently they arise from fusions of primary lysosomes with melanin granules which are already enlarged from multiple fusions among melanosomes. Therefore, the giant granules are not primary lysosomes, nor are they simply enlarged melanin granules as suspected from light microscopic studies. A deficiency of primary lysosomes in the pigment epithelium results, suggesting a defect in intracellular digestion similar to that found in the leukocytes of Chediak-Higashi patients and several animal models. Affected humans probably have defective digestion in their retinal pigment epithelium also; which could impair the renewal process for rod outer segments. Thus, Chediak-Higashi patients may show an increased susceptibility to light damage due not only to hypopigmentation, but to defective intracellular digestion, as well.