Loss of Scotopic Contrast Sensitivity in the Optomotor Response of Diabetic Mice

Abstract

PURPOSE. Diabetes reduces retinal and visual sensitivity to dim light flashes. However, the impact of diabetes on contrast sensitivity in dim light is unknown. Based on the lowered visual sensitivity previously observed, we hypothesized that contrast sensitivity would similarly be reduced. We therefore examined scotopic contrast sensitivity of the optomotor response in the Ins2 Akita/+ mouse model of type 1 diabetes. METHODS.A longitudinal study of spatial and temporal contrast sensitivity in Ins2 Akita/+ mice and wild-type Ins2 +/+ littermates was conducted. Contrast sensitivity of the optomotor response to rotating gratings of various spatial and temporal frequencies was measured at a dim luminance level (2.6 Á 10 À5 cd/m 2 ) known to elicit rod-but not cone-driven responses.RESULTS. An early, progressive loss in scotopic contrast sensitivity was observed in Ins2Akita/+ mice that was absent from Ins2 +/+ littermate controls. The loss in contrast sensitivity developed over a 3-to 4-month period after the onset of hyperglycemia. Ins2Akita/+ mice exhibited a nonselective 40% loss in sensitivity to all spatial frequencies and a selective loss in sensitivity to fast but not to slow varying gratings (temporal frequencies >0.1 Hz or, equivalently, speeds >3 deg/s). Such losses in sensitivity were prevented by glycemic control with insulin treatment.CONCLUSIONS. An association between a model of type 1 diabetes and scotopic contrast sensitivity of the optomotor response is indicated. Ins2Akita/+ mice exhibit a uniform loss in optomotor contrast sensitivity to all spatial frequencies that, unexpectedly, can be explained as being secondary to a retinal or central loss in sensitivity to high temporal frequencies.

Bone's responses to mechanical loading are impaired in type 1 diabetes

“…3). More severe diabetic symptoms were present in Akita males as found in previous studies [49, 50], which was in agreement with that Akita males had more pronounced reduction in both pancreatic beta-cell functions and serum insulin level [32]. Compared with age- and gender-matched controls, the plasma insulin level in Akita males showed a two-fold decrease at the age of 8 weeks and the pancreatic insulin content exhibited a dramatic 10-fold decrease at the age of 22 weeks [50].…”

Cellular responses following retinal injuries and therapeutic approaches for neurodegenerative diseases

“…However, contrast sensitivity testing is a valuable tool for identifying ocular disease and guiding treatment (Richman et al, 2013). Studies have been conducted on the use of contrast sensitivity to evaluate intraocular lenses, and pathologies such as cataracts, glaucoma, optic neuritis, DR and AMD, among others (Bailey, 1993;Ginsburg, 2006;Howes et al, 1982;Richman et al, 2013;Ross et al, 1984;Umino and Solessio, 2013;Woo, 1985).…”

“…Pigmented animal responses are stronger and easier to recognize than those of albino mice or rats, which do not show clear responses to the optomotor test. The optomotor test has been used as a visual test in different animal models of retinal degeneration (e.g., (Barabas et al, 2011;Umino and Solessio, 2013)). …”

Psychophysical testing in rodent models of glaucomatous optic neuropathy

“…Therefore, using the aforementioned behavioral techniques in rodent models that display disease etiology that is similar to humans, such as the DBA/2 mouse, allows us to conduct studies that obtain valuable information on disease mechanisms and therapeutic strategies at considerably lower cost with more data points. We can use these techniques in mice to evaluate therapeutic intervention in rodent models of disease (Adamus et al, 2012; Cahill et al, 2011; Krempler et al, 2011; Savigni et al, 2013), and RGC axon regeneration (de Lima et al, 2012), test variables such as age and gender (van Alphen et al, 2009), neuronal and RGC disease mechanisms in glaucomatous mice (Burroughs et al, 2011; Feng et al, 2013; Kaja et al, 2011), similar to the assessment of visual deficits in other animal models of disease (Pinto et al, 2007; Pinto et al, 2005; Puk et al, 2009; Richards et al, 2008; Roeser and Baier, 2003; Schmucker and Schaeffel, 2006; Umino and Solessio, 2013). Such data contribute to the pre-clinical development of promising therapeutic interventions prior to human clinical trials and benefit from their non-invasive and comprehensive nature resembling many of the aspects of human clinical trials.…”