Abstract
Abstract: :
Purpose: Function and survival of retinal cells are dependent on a normal blood–retina barrier (BRB). Pericytes and vascular smooth muscle (SM) cells surrounding retinal vessels are important in maintaining the BRB. Recently it has been demonstrated that although SM α–actin null mice appear phenotypically normal, they have a highly compromised vascular contractility, tone, and blood flow due to alterations in pericyte and vascular SM cell contractile function. We have used SM α–actin null mice to investigate the effect alteration in pericyte and vascular SM function has on BRB permeability and retina function. Methods: To determine the effect lack of SM α–actin has on vascular permeability, retinal vascular permeability was measured using the Evans blue method. To determine the effect lack of SM α–actin has on retina function, electroretinography (ERG) was performed. Results: At 8 weeks of age, vascular permeability in the retina was 0.0842 ± 0.0157 (mean ± SD, n=6) µg of Evans blue dye per mg of total protein in the retina of SM α–actin null mice, which is significantly higher than that in age–matched wild–type controls (0.0517 ± 0.0170, n = 7, P < 0.001). This result indicates that lack of SM α–actin alters BRB and thereby vascular permeability. ERG functional analysis showed a significant reduction (25%) in scotopic ERG a–wave as early as postnatal day (P) 25. Although this reduction progressed with age, by P75 animals still retained ∼65% of their a–wave amplitude. However, photopic ERG b–wave amplitudes, a reflection of cone function, were more affected. By P25 SM α–actin null mice retained only 55% of their normal litter mates amplitudes and about 50% by P75. Conclusions: These results indicate that lack of SM α–actin alters the BRB, suggesting that normal contractile pericytes and vascular SM cells play an important role in maintaining a functional BRB. Increased permeability observed may be responsible for loss of retinal function in SM α–actin null mice; however, since we did not perform any ERGs at earlier time points than P25, it is possible that the reduced functional competence of the retina is a reflection of delayed development. These results are important in understanding maintenance and function of the BRB and may provide a model for pathological conditions, such as diabetes, that alter the function of this barrier. In addition, these mice provide a new and unique model for examining the role of SM α–actin in BRB function, a previously unexplored area.
Keywords: retina • retinal degenerations: cell biology