[Analysis on the trend of innovation and development in the field of ophthalmology].

Objective: To systematically analyze the innovation and development trend in the field of ophthalmology. Methods: The latest ophthalmology funding program from the National Eye Institute and National Natural Science Foundation of China, and funding project for 2012 to 2016 from the National Institutes of Health, National Natural Science Foundation of China and National key research and development plan of China was collected. Using the comparative analysis method, the major ophthalmology funding areas at home and abroad were analyzed. Papers published in 2012 to 2016 in the field of ophthalmology were collected from the Web of Science Core Collection, among which ESI highly cited papers and hot papers were particularly selected. Using bibliometric methods, the time trend of the number of papers and the citation frequency were analyzed. Using the co-occurrence cluster analysis method, the continued focuses and emerging concerns of ophthalmology papers was analyzed. Results: The funding plan of the National Eye Institute mainly covers nine major diseases in ophthalmology. NSFC focuses on retinal damage and repair mechanisms. The National Key Research and Development Program of China focuses on research on high-end ophthalmic implants. NIH continues to focus on the molecular mechanisms of blinding eye disease such as diabetic retinopathy, age-related macular degeneration, glaucoma, corneal disease and cataracts, basic research in genetics, and advanced diagnostic techniques such as imaging. Latest areas of interest involve gene editing techniques and the application of stem cell technology in ophthalmology. In China, research and application of stem cells in ophthalmic diseases, intraocular sustained-release drug carrier, and precision medicine research in ophthalmology are emerging areas of funding. In 2012 to 2016, research topics of 168 papers collected by ESI focused on macular degeneration, retinal diseases, glaucoma and other eye diseases. How to quickly promote new drugs and new technological achievements to the clinical application is a problem in the field of ophthalmology. How to change the ophthalmology clinic model, so as to provide patients with convenient and quality service, has become a research topic that needs to be given attention to. Conclusions: Based on the multidimensional analysis of innovation and development in the field of ophthalmology, cross application and integration of ophthalmology and high - tech fields such as advanced imaging technology, stem cell technology, gene editing technology, molecular targeting, and artificial intelligence will provide a strong basis for the enhancement of China's ophthalmology research innovation and international competitiveness. Research efforts for ophthalmic transformation should be strengthened, in order to realize the clinical application of the achievements as soon as possible. (Chin J Ophthalmol, 2018, 54: 452-463).

Heterogeneity of endothelin ETA receptor-mediated contractions in the rabbit saphenous vein.

The involvement of endothelin ETA receptors in endothelin-1-induced contractions of the rabbit saphenous vein was studied. After desensitization of endothelin ETB receptors by pretreatment with sarafotoxin S6c, endothelin-1 and sarafotoxin S6b and a high concentration of endothelin-3 caused dose-dependent contractions. However, endothelin-1-induced contractions were much less sensitive to an endothelin ETA receptor antagonist, BQ-123 (cyclo (-D-Asp-L-Pro-D-Val-L-Leu-D-Trp-)), than sarafotoxin S6b-induced responses. The pA2 values of BQ-123 for endothelin-1- and sarafotoxin S6b-induced contractions were 5.69 and 7.65, respectively. These results suggest pharmacological heterogeneity of endothelin ETA receptors in the rabbit saphenous vein.

Endothelin ETA and ETB receptors mediate endothelin-1-induced apamin-sensitive relaxation in the guinea pig ileum.

Endothelin (ET) receptors involved in ET-1-induced responses of the longitudinal muscle of the isolated guinea pig ileum were studied. ET-1 caused concentration-dependent contractions, while ET-3 and selective ETB-receptor agonists, IRL1620 and sarafotoxin 6c (S6c), showed little or no effect. The ET-1-induced contractions were antagonized by BQ-123, an ETA-receptor antagonist, or PD142893, an ETA/ETB-receptor antagonist, indicating that the contraction is mediated by the ETA receptor. In preparations precontracted with carbachol, ET-1 elicited relaxations at lower concentrations and contractions at higher concentrations. ET-3, IRL1620 and S6c caused relaxations. These relaxations were little affected by BQ-123, but greatly antagonized by PD142893. The ET-1-induced relaxations were slightly affected by BQ-788, an ETB-receptor antagonist, but were markedly inhibited by the combination of BQ-788 and BQ-123. In ETB receptor-desensitized preparations, ET-1-induced relaxations were antagonized by BQ-123, whereas ET-3, S6c and IRL1620 showed no response. All these relaxations were abolished by apamin. These results indicate that ETA and ETB receptors mediate relaxation of the ileal smooth muscle through activation of apamin-sensitive K+ channels.

Two different endothelin B receptor subtypes mediate contraction of the rabbit saphenous vein.

To study endothelin receptor subtypes that mediate venous smooth muscle contraction, effects of some endothelin receptor agonists and antagonists on the rabbit lateral saphenous vein were examined and compared with those on the saphenous artery. In the artery, endothelin (ET)-1 elicited concentration-dependent contractions, while selective ETB-receptor agonists, IRL1620 (Suc-[Glu9,Ala11,15]ET-1(8-21)) and sarafotoxin 6c (S6c) had almost no effect. The ET-1-induced responses shifted in parallel to the right by BQ-123 (cyclo (-D-Trp-D-Asp-Pro-D-Val-Leu-)), an ETA-receptor antagonist, or PD142893 (Ac-D-Dip-Leu-Asp-Ile-Ile-Trp), an ETA/ETB-receptor antagonist, indicating the involvement of the ETA receptor in this response. In the saphenous vein, not only ET-1 and ET-3, but also ETB-receptor agonists, IRL1620, S6c and [Glu9]sarafotoxin 6b ([Glu9]S6b), produced concentration-dependent, BQ-123-insensitive contractions. PD142893 did not affect the ET-1-induced contraction, but it shifted greatly the IRL1620-induced concentration-response curve in parallel to the right. The major components of ET-3-, S6c- and [Glu9]S6b-induced contractions were resistant to PD142893. These results indicate that two different vasoconstrictive ETB-receptor subtypes, ETB1 (sensitive to IRL1620 and PD142893) and ETB2 (insensitive to IRL1620 and PD142893), are located on the smooth muscle of the saphenous vein.