Common pathophysiology affecting diabetic retinopathy and Parkinson's disease

Diabetic retinopathy (DR) is the leading cause of irreversible vision loss in adults. Parkinson's disease (PD) is a chronic progressive neurodegenerative movement disorder characterized by progressive loss of dopaminergic neurons in substantia nigra of midbrain. Evidences suggest that diabetic patients tend to show higher incidence of PD, advocating a shared mechanism between both the diseases. Interestingly, disruption of the dopaminergic system, which is an important causative factor in PD, has also been observed in DR. It is reported that retinal dopamine and tyrosine hydroxylase protein levels are downregulated, and dopaminergic amacrine cells appear to be degenerating in the animal models of DR. Further, injecting the diabetic mice with dopamine-restoring or dopamine-activating drugs already used to treat PD can restore dopamine levels and significantly improve diabetes-associated visual dysfunction in the early stage. Conversely, drugs already in use for insulin resistance also show protective effects in PD. Furthermore, α-Synuclein pathology of PD can be induced solely by high glucose in diabetic animal models. In conclusion, these findings establish an important role of dopamine deficiency as a common contributing factor in DR and PD. The changes in the ocular of diabetes involve dopamine metabolism disturbance, mimicking PD at the molecular level. Consequently, we could consider DR as at least partially the PD like molecular pathology in the eye. Importantly, indicating that dopamine decrease may play a role in DR will lead to a better understanding of the high rate of comorbidity reported between diabetes and PD, and reveal new therapeutic avenues for DR and other disorders that involve dopamine deficiency.