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DISCUSSION
As the population grows older, more and more eye diseases become apparent. Many are related to the malfunction of ocular blood flow, in particular AMD, which is the leading cause of severe, irreversible visual loss in elderly Americans [10].
Current major treatments for AMD include laser photocoagulation, transpupilary thermotherapy, radiotherapy, submacular surgery, photodynamic therapy with verteprofin, etc [1113]. As these treatments are limited in various aspects, the search for more effective treatments is urgently needed. The emerging pharmacological therapy provides a new direction for the treatment of AMD.Table 1Chemical structures of (R, R)XY and (略)Table 2Effects of (R, R)XY compounds on choroid blood flow (略)Table 3Effects of (R, R)XY compounds on ciliary body blood flow(略)Table 4 Effects of (R, R)XY compounds on iris blood flow(略)
The reason that the CNV is formed in 2/3 of AMD patients is mainly because of the malfunction of choroidal circulation during the early stage of AMD, resulting in a decrease of the blood flow of choriocapillaries. Chain reactions are triggered which lead to retinal pigment epithelium degeneration, Bruchs membrane breakdown, CNV formation, AMD development and blindness in the end [9,11]. To prevent its occurring, improvement andfacilitation of choroidal blood flow is necessary. A large number ofcompounds, natural [1420] as well as synthetic [6,7,9,2123] have been found to affect the ocular blood flow. It is hoped that they could become useful to the treatment/prevention of glaucoma, ischemic retinopathy and AMD. Among them, NO donors have been found to be most promising. It is well established that NO can cause vasodilation and increase in blood flow in general [5,24].
Furthermore, the relationship among chemical structures, geographic and optic isomers of compounds and their effects on ocular blood flow has been gradually established [9,1621]. It has been reported that ZX5, trans1phenyl3{3methoxy2propoxy5[4(3,4,5trimethoxyphenyl)1,3dithiolane2yl]phenyl}thiourea, could increase choroid blood flow stereospecifically in rabbit eyes[25]. The increase of choroid circulation could be due to the release of NO in the choroid.
The N1position modification of (R, R)ZX5 and (S, S)ZX5 resulted in the compounds of (R, R)XY and (S, S)XY. Four out of all twentyfour compounds tested, (R, R)XY1, (R, R)XY3, (R, R)XY8 and (R, R)XY9, have been shown to significantly increase the blood flow in choroid. Among them, (R, R)XY1 and (R, R)XY9 seem to be the most potent compounds. All these four effective compounds are (R,R)XY series. Their corresponding enantiomers did not show any effect on the blood flow, and actually none of (S, S)XY isomers affects the blood flow. As for (R, R)XY isomers, not all compounds increased the blood flow. This may be due to different R groups of chemical structures which result in different steric hindrance. Just like (R, R)ZX5, (R, R)XY compounds could also induce increase of ocular blood flow, through release of NO.
These results indicate that (R, R)XY compounds could become a new class of pharmaceutical agents for the prevention/treatment of eye diseases related to ocular blood flow. Further researches on these compounds are warranted.
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