Table 1.
Experimental studies on the ophthalmological application of H2.
| Ocular Diseases |
Experimental Objects | Disease Models | Methods of H2 Uptake | Effect of H2 | Refs. |
|---|---|---|---|---|---|
| Dry eye disease | Wistar rats | Scopolamine-induced DED | Intraperitoneal injection of HRS (0.6 mmol/L) at a dose of 5 mL/kg BW daily for 28 days; dropping HRS into the eye 1 time per hour, 9 times per day | Inhibiting the activity of NF-kB to reduce inflammation | [36] |
| Alkali burn of cornea | SOD-1−/− mice or WT mice | Alkali burn | Irrigated with HRW (0.5–0.6 ppm) onto the cornea for 30 min | Reducing oxidative stress; inhibiting angiogenesis in cornea | [37] |
| Wistar rats | Irrigated with HRW (1.2–1.6 ppm) onto the cornea for 5 min | Upregulating the expression of antioxidants | [38] | ||
| UVB | SOD-1−/− mice or WT mice | Ultraviolet B ray-induced corneal damage model | Irrigated with HRW (0.5–0.6 ppm) onto the cornea | Reducing oxidative stress; inhibiting of angiogenesis in cornea | [37] |
| Corneal endothelial dysfunction | Rabbits | MNU-induced corneal endothelial cell injury | Irrigated with HRS (1.2 ppm) 3 times a day for 3 min and 3 drops per second for 7 days | Anti-apoptotic effect through the NF-κB/NLRP3 and FOXO3a/p53/p21 pathway | [39] |
| Rabbits | Corneal endothelial dysfunction induced by phacoemulsification | Ultrasound oscillation with irrigation solution at almost 61% H2 dissolved concentration for 30 s | Reducing oxidative stress | [40] | |
| Cataract | Rats | Selenite-induced cataract | Intraperitoneal injection of HRS (0.6 mmol/L) at a dose of 5 mL/kg BW daily from postnatal day 8 to postnatal day 17 | Maintaining the activity of antioxidant enzymes, inhibiting lipid peroxidation | [41] |
| Uveitis | Rats | Endotoxin-induced uveitis | Inhaling mixed gas that consisted of 67% H2 and 33% O2 for once a day for 3 weeks | Suppressing the microglia activation | [42] |
| Rats | Intraperitoneal injection of HRS (0.6 mM) at a dose of 10 mL/kg BW once a day for 1 week | Maintaining the integrity of the blood–aqueous barrier | [43] | ||
| RP | Rats | Rd6 rats | Drinking HRW (1.2–1.6 ppm) 3.42 ± 0.14 mL/day for 1 week | Neuroprotective effect | [44] |
| Rats | MNU-induced RP | Intraperitoneal (10 mL/kg BW) and intravitreous (8 μL) injections of HRS (0.6 mmol/L) | Increasing the level of SOD, modulating the expressions of apoptosis-related genes | [45] | |
| DR | Male rats | Rats with streptozotocin-induced diabetes mellitus | Intraperitoneal injections of HRS (0.86 mmol/L) at a dose of 5 mL/kg BW daily for 1 month | Reducing oxidative stress; preserving synaptophysin and BDNF levels | [46] |
| C57BL/6J mice | Rats with diabetes mellitus | Intraperitoneal injections of HRS | Reducing the retinal neovascularization, and the expression of VEGF and MDA | [47] | |
| Glaucoma | Rats | Retinal ischemia/reperfusion | Consecutive peritoneally injected of HRS (0.6 mM) at a dose of 5 mL/kg BW until the rats were sacrificed | Alleviating apoptosis of RGCs by overactivating PARP-1 | [48] |
| Inhaling mixed gas that consisted of 67% H2 and 33% O2 for 1 h daily for 7 days | Lessening RGCs loss; reducing the levels of IL1-β, TNF-α and 4-HNE | [49] | |||
| AMD | Mice | NaIO3-induced AMD | Intragastric administration of HRS (4.0 mg/L) at a dose of 10 mL/kg BW for 12 days. | Inhibiting cellular senescence; maintaining DNA homeostasis | [50] |
| Intragastric administration of HRW (0.55~0.65 mM) at a dose of 1 mL/g three times daily for 12 days | Inhibiting oxidative stress and apoptosis | [51] | |||
| Laser-induced CNV mouse | Inhaling mixed gas that consisted of 21% oxygen, 42% H2 and 37% nitrogen gas for 2/5 h daily for 15 days | Alleviating CNV leakage | [52] | ||
| Light-induced retinal damage | Rats | Blue light-induced damage model | Intraperitoneal injection of saturated HRS (0.6 mmol/L) at a dose of 1 mL/100 g BW once a day before and during the exposure session | Suppressing photo-oxidative stress | [53] |
| Intraperitoneal injection of saturated HRS(5 mL/kg) before and within 5 days after light exposure | [54] | ||||
| Optic nerve injury | Rats | Establishing the optic nerve crush model via surgery | Intraperitoneal injection of saturated HRS (5 mL/kg) at 6:00 and 18:00 lasting for 2 weeks | Reducing the lipid peroxidation and apoptosis of RGCs | [55] |
| Guinea pigs | Glutamate-induced retinal injury model | Intravitreous (almost 0.6 mmol/L) and/or peritoneal injection (5 mL/kg) of HRS | Clearing glutamate by increasing EAAT-1; reducing RGCs apoptosis of by upregulating GRP78 | [56] | |
| RGCs cells | S-nitroso-N-acetylpenicillamine-induced oxidative stress model | Culturing cell in medium consisting of 5% O2 and 95% H2 (v/v) for 24–72 h | Suppressing ONOO−-mediated oxidative stress by clearing peroxynitrit | [57] |
Abbreviations: H2, molecular hydrogen; DED, dry eye disease; HRS, hydrogen-rich saline; NF-κB, nuclear factor kappa B; SOD-1, superoxide dismutase-1; HRW, hydrogen-rich water; MNU, N-Nitroso-N-methylurea; NLRP3, NOD-like receptor family pyrin domain containing 3; FOXO3a, forkhead box O3; BDNF, brain-derived neurotrophic factor; VEGF, vascular endothelial-derived growth factor; MDA, malondialdehyde; AMD, age-related macular degeneration; CNV, choroidal neovascularization; EAAT-1, excitatory amino acid transporter 1; RGCs, retinal ganglion cells; GRP78, glucose-regulated protein 78; WT, wild-type; BW, bodyweight; ONOO−, peroxynitrite.