Retinal arterial tone is controlled by a retinal-derived relaxing factor

The present study provides evidence that retinal tissue may profoundly influence the retinal arterial smooth muscle cell tone by releasing an unknown retinal relaxing factor. Isolated bovine retinal arteries with and without adhering retinal tissue were mounted in a wire myograph for isometric tension recordings. The maximal contraction induced by prostaglandin F-2 alpha was 0.95+/-0.7 mN (n=6) in the presence and 5.15+/-0.76 mN (n=6) in the absence of adhering retinal tissue. The contractions induced by U-46619, serotonin, and endothelin-l were similarly blocked in the presence of retinal tissue. The K+ 120 mmol/L-induced contraction was not significantly affected (2.8+/-0.7 mN, n=6, in the presence and 3.6+/-0.7 mN, n=6, in the absence of retinal tissue). Placing a piece of bovine retinal tissue in the proximity of a contracted (ie, with prostaglandin F-2 alpha) retinal artery induced a complete relaxation of the retinal vessel, suggesting the involvement of a diffusible chemical vasorelaxant. Also porcine, canine, and ovine retinal tissue completely relaxed the contracted (with prostaglandin F-2 alpha) bovine retinal artery. Other smooth muscle preparations, including rat mesenteric and renal arteries and rat main bronchi, also relaxed with the application of a piece of bovine retinal tissue. Incubation of bovine retinas in a Krebs-Ringer bicarbonate solution yielded a solution that relaxed isolated precontracted bovine retinal arteries, confirming the involvement of a diffusible chemical messenger. Hexane extraction, heating the solution to 70 degrees C, or treatment with trypsin did not alter the relaxing properties of the incubation solution. The characteristics of the retinal relaxing factor do not correspond with those of nitric oxide, prostanoids, adenosine, acetylcholine, or any other of the known vasoactive neurotransmitters released from the retina. Our results suggest that retinal arterial tone is controlled by a diffusible, hydrophilic, and heat-stable relaxing factor that does not correspond with a known vasoactive molecule formed within the retina.