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D. Everhart, K. Cusato, R. B. Barlow; Acute Hypoglycemia Impairs Visual Function in Mice. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5187. doi: https://doi.org/.
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Determine the effects of insulin and fasting-induced hypoglycemia on C57BL/6J mouse visual function and gene expression.
Intraperitoneal injection of C57BL/6J mice with 1.5U/kg of Insulin lispro, a fast-acting insulin analog, lowered blood glucose (BG) from ~130 to ~65 mg/dL in 30 min. Fasting C57BL/6J mice lowered BG to ~70 mg/dL in about 3 days. Two-alternative, forced choice optomotor behavioral methods (modified OptoMotry, CerebralMechanics, Lethbridge, AB, Canada) were used to assess the visual acuity and contrast sensitivity of insulin-treated (n=4), fasted (n=4), and saline-treated (n=4) C57BL/6J mice. Visual function was measured 30 and 150 minutes following injection and 3 days following fasting. Retinas were then harvested and total RNA was extracted for gene expression profiling using Affymetrix GeneChip Mouse Genome 430A 2.0 microarrays.
Reaching similar levels of hypoglycemia, rapidly (<1hr) and slowly (~72 hrs) produced dissimilar effects on both visual function and gene expression. Insulin-injected mice lost 35.1% acuity and 86.7% contrast sensitivity on average, whereas fasted mice did not show significant changes. The behavioral results and ERG data from insulin-treated and fasted mice agree: insulin-treated mice exhibit significant losses in both visual and retinal function 30-45 minutes following injection, whereas saline-treated mice did not. Microarray analysis reveals changes in gene expression that may yield insights into hypoglycemia-induced changes in the retina.
Insulin-induced hypoglycemia in mice causes significant losses in visual function and changes in gene expression. The relationship between glucose and vision may highlight the importance for glycemic control in diabetics and diseases related to metabolic stress such as macular degeneration.
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