Inhibitors of Crystallin Aggregation

Cataract is one of the leadings causes of vision loss worldwide. The exact mechanism is unknown, but aggregation of crystallin proteins, which make up much of the protein content of the lens and are involved in maintaining the integrity of the lens, leads to the characteristic clouding of the lens. Given this, it is of great clinical importance to identify possible inhibitors of crystallin aggregation. Phthalocyanine compounds are known to inhibit aggregation of proteins such as tau and α-synuclein, which are related to neurodegeneration. Their effectiveness as inhibitors of crystallin aggregation has not been evaluated. To characterize the potential of phthalocyanines as inhibitors of crystallin aggregation, fluorescence proteostat aggregation assays and transmission electron microscopy (TEM) were used to detect the presence of aggregation via β-sheet character and determine specific aggregation morphology respectively. It was determined that porphyrazine 285 (PZ285) exhibited poor inhibition of crystallin aggregation due to its minimal solubility in aqueous solution. Phthalocyanine tetrasulfonate (PcTS) showed some reduction in crystallin aggregation in a concentration-dependent manner.