# Plant Iridoids Affect Intraocular Pressure and Vascular Flow in the Rabbit Eye
## 4 Discussion  
To date, there are remarkably few reports that describe the direct effects of applying both plant extracts and isolated pure substances to the eye. Forskolin, a natural compound from the labdane diterpene group isolated from _Plectranthus barbatus_, was tested in experimental therapy in an open-label study [14] in patients with open-angle glaucoma. Research conducted in 90 adult patients has proven a decrease in IOP after 4 weeks of ocular admin  
Figure 4: Iris blood flow (flux, a.u.) before and 1, 2, 3 and 6 h after administration of a 0.5% iridoid solution. The graph shows the difference in flow values compared to the first baseline measurement. Timolol was administered as a reference at 0.5%. Positive values indicate an increase in iris blood flow. An asterisk indicates a statistically significant effect. Verb: verbenalin; Loga: loganin, Aucu: aucubin; Catal: catalpol; Harp: harpagoside; Oleeu: oleuropein; Gencj: gentiopicroside; Seco: secologanin; Tim: timolol. Figure 5: Iris blood flow (flux, a.u.) before and 1, 2, 3 and 6 h following administration of a 0.1% iridoid solution. The graph shows the difference in flow values compared to the first baseline measurement. Timolol was administered as reference at 0.5%. Positive values indicate an increase in iris blood flow. An asterisk indicates a statistically significant effect. Verb: verbenalin; Loga: loganin, Aucu: aucubin; Catal: catalpol; Harp: harpagoside; Oleeu: oleuropein; Gencj: gentiopicroside; Seco: secologanin; Tim: timolol. istration by 5.4 mm Hg. Forskolin, by increasing cAMP, could help improve fluid drainage through the trabecular meshwork, reducing pressure inside the eye [15; 16]. Cannabinoids (cannabidiol and tetrahydroccannabinol) in nanoemulsions containing Carbopol(r) 940 NF at a concentration of 1% significantly reduced IOP by 4.5 mm Hg in eyes treated for up to 360 min in a _Dutch Belted_ male rabbit model [17]. A possible mechanism of cannabinoids is an interaction with the CB1 and CB2 receptors in ocular tissues, which affects fluid outflow and reduces IOP. Contrary to the above-mentioned results, 0.4% and 1.6% nanoemulsions of cannabinoid in polysorbate 80 and medium-chain triglyceride exhibited no effect on IOP in a mouse model. Experimental eye drops containing cannabinoids have been sold on Jamaica, but no extensive results have yet been delivered [18]. The results of the topical ophthalmic administration of pure tetrahydroccannabinol are not clear at this time. [PERSON] et al. found no effect of 1% THC on changes in IOP pressure [19]. The lack of THC activity was also repeated in other experiments by [PERSON] [20]. In contrast to these results, the formulation in tocrisolve (a mixture of phospholipids and ethanol in water) with Pluronic-F68 stabilized commercial soybean oil emulsion presented a 28% reduction in IOP in the eighth hour after administration in a mouse model [21]. Interestingly, the effect of cannabinoids was sex-dependent. The authors concluded that THC lowers IOP by activating two receptors, CB1 and GPR18. [PERSON] et al. found reduced the IOP peak by after 2 h and 47% after 4 h of administration of THC eye formulations containing mono- and di-valine esters as auxiliary substances [22]. [PERSON] et al. proved that topical administration of drops containing 0.2% trans-resveratrol (bioactive compound present in red grapes, red wine, _Fallopia japonica_) in 3% polyvinylpyrrolidone decreased the IOP by 30% in rats with steroid-induced ocular hypertension [23]. In the experiment, resveratrol enhanced ocular blood flow and reduced oxidative stress in the trabecular meshwork, improving fluid outflow and lowering pressure. [PERSON] investigated eydrops containing 0.43% curcumin (isolated from _Curcuma longa_) in a nanoemulsion with Pluronic-F127 stabilized tocopherol polyethene glycol 1000 succinate nanoparticles, reducing hypertension in cobalt chloride-induced hypoxia in rats [24]. More reports can be found regarding experiments in which natural substances were supplemented orally. [PERSON] et al.