Purchase this article with an account.
Kosha Dholakia, Andres Guevara-Torres, Jesse B Schallek; Early changes in blood cell flux in retinal capillaries of diabetic and healthy mice imaged in vivo. Invest. Ophthalmol. Vis. Sci. 2020;61(7):806.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Capillary dysfunction is an early manifestation of diabetic retinopathy, however the microscopic size of capillaries makes them challenging to study in vivo. Advances in adaptive optics scanning light ophthalmoscopy (AOSLO) have enabled detailed counts of single red blood cells (RBC) in capillaries of the living eye. Here, we track the same capillaries in healthy and hyperglycemic mice for 3 months to determine if there are changes in RBC flux and stasis in early diabetes.
We imaged retinal capillaries of 18 anesthetized male mice on a C57BL6/J background. 9 mice were hyperglycemic (blood glucose (BG) >250 mg/dL; Fig 1) from a mutation leading to misfolded insulin (Ins2Akita+). 9 littermates were euglycemic (BG 120-250 mg/dL) and imaged as controls. Capillaries were mapped in the superior-temporal retina (7-22 degrees of eccentricity from the optic disc). RBC flux was measured with a custom AOSLO with offset aperture phase contrast imaging by placing a 15 kHz line scan across each capillary (Guevara-Torres et al., 2016). We reimaged 79 unique capillaries in hyperglycemic mice and 97 in healthy mice from postnatal week 5-18 at biweekly intervals. RBCs were manually counted for 1 s in each capillary.
Ins2Akita+ mice showed elevated BG as early as postnatal week 3-5 (BG=319±97 mg/dL (ave±SD)) compared to euglycemic mice (BG=212±49 mg/dL). RBC measurements were grouped into two epochs: young adults (5-10 wks) and mature adults (13-18wks). In young adults, there was a difference in mean RBC flux between hyperglycemic and euglycemic mice (p=0.003; paired t-test). There was no significant difference in flux between the two groups in mature adults (p=0.25). Flux decreased in both groups as mice aged, however hyperglycemic mice showed a greater decrease in flux (21% vs 11%, respectively). No striking difference in capillary stalls was observed (1.5% in hyperglycemic, 1.3% in euglycemic mice) each comparable to rates reported in the brain (Erdener et al. 2017).
This represents the first study where retinal RBC flux has been non-invasively tracked in the same capillaries over disease progression. These events may reveal some of the first changes in the diabetic retina that are impossible to study with histology and may be overlooked with large vessel study. Noninvasive imaging has the potential to show progression of disease and, in the future, measure response to therapy.
This is a 2020 ARVO Annual Meeting abstract.
This PDF is available to Subscribers Only