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Purpose: The effects of chronic chloroquine administration on serum proteins and free amino acids of rabbits and the accompanying ultrastructural changes in the retina were investigated., Methods: Thirty pigmented rabbits were injected intramuscularly with chloroquine diphosphate (14 mg/Kg bw). Fifteen rabbits served as control. Blood samples drawn after 1, 2, 3, 4, 5, 6 and 12 months were assayed for serum proteins by Bio-analytic kits and horizontal electrophoretic technique. Free amino acids were determined by Beckman analyzer. Central retinal tissue was fixed in 4% glutaraldehyde, embedded in araldite CY212 and sectioned for ultrastructural examination., Results: Histopathologic changes were apparent within three months, initially affecting the pigment epithelium and photoreceptors and later involving the remaining neuroretinal layers. Hypoproteinemia gradually developed mainly due to a sharp drop in albumin and alpha 1 and 2 globulin fractions, inspite of an increase in beta and gamma globulin fractions. The concentration of non-essential amino acids varied considerably from a depletion of taurine, aspartine, glutamine, tryptophan and arginine to an increase of serine, alanine, GABA and ornithine. The most outstanding effect was the disappearance of tyrosine and its return to normal value at the end of the experiment., Conclusion: The disturbances in protein pattern and free amino acid levels are an indication of chloroquine toxicity and may be implicated in the retinopathy.

The effect of long-term treatment of chloroquine (CAS 54-05-7) (20 mg/kg body weight) on serum lipid components and its relation to to the retinotoxic effect was studied in albino rats. Chloroquine was found to form lamellar lysosome-like structures within the photoreceptive layer, as well as the pigment epithelium and neurooretinal layers. Biochemically, hypolipidemia in the serum was observed mainly due to the decrease in phospholipid portion. It was hypothesized that due to the inhibition of the degradation process in the defective lysosomes, the retinal cells were denied the re-use of their own phospholipids, and thereby resort to their uptake from the serum.