Deletion of smooth muscle alpha-actin alters blood-retina barrier permeability and retinal function.
OBJECTIVE
Vascular smooth muscle (SM) cells and pericytes are essential for normal vascular development. SM alpha-actin null mice were used to determine whether vascular SM and pericyte contractile functions, and not merely their presence, are necessary for vascular development, normal blood-retina barrier (BRB) permeability, and retinal function.


METHODS
Age-matched SM alpha-actin null and wild-type mice were analyzed. Retinal structure, vascular pattern, and SM cell and pericyte distribution were analyzed histologically. Retinal vascular permeability (RVP) was measured with the Evans blue dye method. Electroretinography (ERG) was performed to evaluate retinal function.


RESULTS
Deletion of SM alpha-actin did not result in any alterations in retinal morphology, vascular pattern, or SM cell and pericyte ensheathing of vessels in SM alpha-actin null mice. A significant increase in RVP was observed in SM alpha-actin null mice at both postnatal day (P)50 and P75 (P<0.05 and P<0.001, respectively). ERG analysis demonstrated a significant reduction in both rod and cone function in SM alpha-actin null mice at P22, P45, and P75 (P<0.01 at all ages).


CONCLUSIONS
These results demonstrate that SM alpha-actin in SM cells and pericytes is not necessary for the formation of a normal retinal vascular pattern; however, SM alpha-actin is necessary for SM cells and pericytes to interact with endothelial cells to form a fully functional BRB. These results are important in understanding the role of contractile gene expression in the maintenance and function of the BRB and may provide a model for studying pathologic conditions, such as diabetes, that alter the function of this barrier.
Tomasek
James J
JJ
Departments of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City 73104, USA. james-tomasek@ouhsc.edu
Haaksma
Carol J
CJ
Schwartz
Robert J
RJ
Vuong
Duc T
DT
Zhang
Sarah X
SX
Ash
John D
JD
Ma
Jian-xing
JX
Al-Ubaidi
Muayyad R
MR
D000199:Actins / Q000502:physiology*; D000418:Albumins / Q000378:metabolism; D000818:Animals; D001813:Blood-Retinal Barrier / Q000502:physiology*; D015153:Blotting, Western; D002199:Capillary Permeability / Q000502:physiology*; D004596:Electroretinography; D020868:Gene Silencing / Q000502:physiology*; D007124:Immunoenzyme Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D020286:Pericytes / Q000502:physiology; D012160:Retina / Q000502:physiology*; D012171:Retinal Vessels / Q000378:metabolism*
D000199:Actins; D000418:Albumins