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Ophthalmic Disease

Glaucoma is an eye disease that ultimately damages the optic nerve, resulting in loss of vision. There are about 3 million US citizens affected by open-angle glaucoma (OAG); of these, more than 120,000 are blind accounting for between 9 and 12% of all blindness due to ophthalmic diseases. The National Eye Institute projects that by 2030 about 4.2 million people will suffer of glaucoma, a 58% increase compared to today's number. Worldwide, glaucoma affects 67 million people, 10% of whom are bilaterally blind (Mantravadi 2015).

  • glaucoma

  • lens opacification

  • diabetic retinopathy

  • age-related macular degeneration

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Glaucoma encompasses a group of irreversible and eventually blinding eye diseases which are characterized by progressive degeneration of retinal ganglion cells and the optic nerve. Risk factors for glaucoma include increased intraocular pressure, high blood pressure and ageing. There is evidence that free-radical mediated oxidative cell damage is a contributing factor (Izzotti 2006, Chrysostomou 2013, Patil 2017).

If treated early, it is possible to slow or stop disease progression with medication, laser treatment or surgery; the goal of these treatments is to decrease eye pressure and thereby prevent damage to the optic nerve. Nonetheless, OAG remains one of the leading causes of vision loss in the US, and the second leading cause of blindness globally (Patil 2017).

The term “cataract” refers to gradual clouding (opacification) of the crystalline lens of the eye, leading to vision impairment and, eventually, vision loss in the absence of effective treatment. Currently there are no drugs to treat cataracts and surgery is the main approach for treatment (Opere 2018).

In the US, cataracts occur in 68% of those over the age of 80. By age 75, half of white Americans have cataract, which translates into about 7.5 million people. The NIH estimates that the number of Americans suffering from cataracts will reach approximately 50 million by 2050. Cataracts cause half of all cases of blindness and 33% of visual impairment worldwide, according to the WHO.

Diabetic retinopathy (DR) is the most common microvascular complication of diabetic patients and one of the main causes of acquired blindness in the world.

 

Over 400 million people worldwide suffer from type 2 diabetes, and more than 45% of them have DR (Calderon 2017). DR is the result of both inflammation and oxidative damage (mediated by reactive oxygen species)to the small blood vessels and neurons of the retina: retinal tissue is exceedingly susceptible to oxidative damage on account of exposure to light, uniquely high oxygen consumption, and high-energy demand requiring high levels of mitochondrial reactive oxygen species generation (Si 2013, Calderon 2017, George 2018, Domenech 2020).

Age-related macular degeneration (ARMD or AMD) is a condition that results in blurred vision or the absence of vision in the center of the visual field. AMD typically occurs in older people; it is due to damage to the retinal macula, which comprises only about 2.1% of the total retinal area. Even though the macula accounts for such a small fraction of the visual field, almost half of the visual cortex is devoted to processing macular information.

Emerging evidence indicates that two important drivers of AMD are oxidative stress and inflammation. (George 2018, Domenech 2020). As stated in connection with DR, retinal tissue is exceedingly susceptible to oxidative stress for the above-stated reasons.

In 2019, Han et al. published an excellent review article titled “Hydrogen sulfide: a gaseous signaling molecule modulates tissue homeostasis – implications for ophthalmic diseases”; the authors point out that “Under physiologic status, H2S plays a critical role in maintaining cellular physiology and limiting damages to tissues… Detailed investigations have demonstrated that administration of H2S donors could regulate intraocular pressure, protect retinal cells, inhibit oxidative stress and alleviate inflammation by modulating the function of intra or extracellular proteins in ocular tissues” (Han 2019).

Han’s summarizes 165 studies under the following headings:

  • Generation of H2S in ocular tissues

  • H2S and glaucoma: Reduction of intraocular pressure

  • H2S and glaucoma: Effect on ocular blood supply

  • H2S and glaucoma: Protection on neurons

  • H2S and diabetic retinopathy: Reduction of the effects of advanced glycation end products (AGEs)

  • H2S and diabetic retinopathy: Inhibition of oxidative stress and inflammation

  • H2S and diabetic retinopathy: Protective effect on retinal neurons

  • H2S and diabetic retinopathy: Multiple effects on retinal blood vessels (dual role of blood-retinal barrier stability, antithrombotic effect, modulation of the retinal blood flow)

  • H2S and retinal degeneration: Modulation and protection of retinal neurons

  • H2S and retinal degeneration: Potential in stem cell transplantation therapy

 

H2S prodrugs, including Sulfagenix’s SG1002, have a considerable therapeutic potential in the ophthalmic field to:

  • Restore homeostasis in eye tissues affected by oxidative stress, inflammation/immune dysfunction, mitochondrial dysfunction, high glucose-induced neuronal senescence, and age degeneration;

  • Counteract thrombosis and stabilize the blood-retinal barrier;

  • Protect eye tissues against ischemia-reperfusion damage (which may affect the retina even in the absence of high intraocular pressure);

  • Regenerate retinal photoreceptors and retinal pigment epithelial cells via increased proliferation and survival of retinal progenitor cells or via transplantation strategies.

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