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In a previous human proteome high-throughput array, we found that \u03b2A3\/A1-crystallin interacts with protein tyrosine phosphatase 1B (PTP1B), a key regulator of glucose metabolism. This prompted us to explore possible roles of \u03b2A3\/A1-crystallin in metabolism of retinal astrocytes. We found that \u03b2A1-crystallin acts as an uncompetitive inhibitor of PTP1B, but \u03b2A3-crystallin does not. Loss of \u03b2A1-crystallin in astrocytes triggers metabolic abnormalities and inflammation. In CRISPR\/cas9 gene-edited \u03b2A1-knockdown (KD) mice, but not in \u03b2A3-knockout (KO) mice, the streptozotocin (STZ)-induced diabetic retinopathy (DR)-like phenotype is exacerbated. Here, we have identified \u03b2A1-crystallin as a regulator of PTP1B; loss of this regulation may be a new mechanism by which astrocytes contribute to DR. 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