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E. C. Steele, Jr.; Diabetic Culture Conditions Alter the Innate Purinergic Responses of Immortalized Rat Mueller (rMC-1) Cells. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1340.
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Traditional studies relating to diabetic retinopathy have focused upon diabetes-induced changes in neuronal and vascular function. However, some recent studies suggest that diabetes alters aspects of normal functioning of Mueller cells, macroglial cells which support and modulate both neuronal and vascular function in the retina. In the present study, we tested whether diabetic culture conditions could directly and acutely alter the response of immortalized rat Mueller (rMC-1) cells to extracellular purinergic agonists, which reflect retinal activity and mediate, in part, Mueller cell-neuronal and Mueller cell-vascular communication.
rMC-1 cell cultures were maintained for 48 hours in control (5 mM glucose + insulin) or diabetic (15 or 25 mM glucose - insulin). Cells were loaded with fura-2 and intracellular free calcium changes in response to purinergic agonists (ATP, ADP, BzBzATP, UTP, UDP) were recorded. Aspects of response profiles (eg- peak amplitudes and total area under the curve) from cells maintained in normal and diabetic conditions were compared using a Student’s t-test with P<0.05 indicating significance.
rMC-1 cells maintained under diabetic conditions exhibited statistically significant differences in their response profiles to some, but not all, purinergic agonists compared to cells maintained under non-diabetic conditions.
Diabetic (hyperglycemic and hypoinsulinemic) conditions directly and acutely alter the normal purinergic responses of cultured Mueller cells. Such changes likely impact Mueller cell-neuronal and Mueller cell-vascular interactions within the retina and contribute to the early stages of development and progression of diabetic retinopathy. Mueller cell purinergic receptors, or their downstream targets, may thus represent novel targets for the development of early intervention or prevention strategies to combat diabetic retinopathy.
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