Cats are affected with mucopolysaccharidosis VI and I (MPS VI, MPS I), two recessively inherited but distinct deficiencies of lysosomal hydrolases [MPS VI=arylsulfatase B (ASB); MPS I=Alpha L-iduronidase (Alpha L-i)]. In MPS VI, the disease in the RPE has been characterized and found to correlate with temporal, spatial and pigment density factors. A similar characterization is proposed for MPS I. In vitro studies in MPS I will determine if the RPE retains the essential features of the in vivo disease. Biochemical studies will characterize the relationship between age and pigmentation factors on the residual enzyme (Alpha L-i) activity. The glycosaminoglycans (GAGs) present in normal RPE and accumulating in diseased (MPS I and VI) RPE will be determined. Synthesis and secretion of GAGs will be measured in cultured cells and correlated with age, pigmentation, spatial position and enzyme activity levels. The effect of the disease on the RPE's ability to synthesize extracellular matrix material and/or type IV collagen will be studied. Experimental modification or """"""""therapy"""""""" of the diseases will be investigated in vivo and in vitro. The relationship between outer segment phagocytosis and/or GAG turnover and disease in the RPE will be determined in vitro. Bone marrow transplantation or enzyme activation (MPS VI-dimerization of ASB with cystamine) will be investigated as potential therapeutic modalities. In vitro studies will be used to screen potential therapies prior to their in vivo use.
