REVERSING GLAUCOMA

Neuroprotection, enhancement and regeneration agents entering clinical trials

Default banner image for REVERSING GLAUCOMA
Photo of Howard Larkin

Several treatments that protect from loss of retinal ganglion cells (RGCs), regenerate axon cells and enhance retinal function are at, or near, the clinical trial stage, Jeffrey L Goldberg MD, PhD told a session of the American Academy of Ophthalmology Annual Meeting in Chicago, USA. In rodent tests, the topical rho-kinase (ROCK) inhibitor Rhopressa (Aerie Pharmaceuticals) showed neuroprotective and neuroregenerative effects, said Dr Goldberg, Professor and Chairman of the Byers Eye Institute at Stanford University, Stanford, California, USA. After traumatic optic nerve injury, treated animals had higher RGC survival rates and more optic nerve axon regeneration than did animals receiving a placebo (Exp Eye Res 2016). However, it is uncertain if topical administration would be effective in humans since topical drug penetration is better in rodents than in primates, Dr Goldberg added. The treatment’s long-term effects, any neuroprotective effect beyond intraocular pressure (IOP) lowering, and its effectiveness across different diseases also are unknown. Adenosine receptor agonists also are in human testing, Dr Goldberg said. Preclinical data suggest Trabodenoson (Inotek Pharmaceuticals) may have a direct neuroprotective effect on RGCs. Stem cells may help treat the retina in two ways. First, they can continuously produce neuroprotective survival and growth factors. Even putting them in the vitreous might slow the course of glaucomatous degeneration, he noted. Second, induced pluripotent stem cells can be implanted 
in the retina and turned into RGCs using gene therapies 
like Sox4 and Math5, Dr Goldberg said. “Not only do they look like retinal ganglion cells, they act electrophysiologically like RGCs.” In a rodent model, RGCs transplanted into uninjured retinas have integrated into the retina, with axons extending back along the optic nerve across the optic chiasm to the lateral geniculate nucleus and superior colliculus, the two major synaptic targets in both rodent and human brains, Dr Goldberg said. The transplanted RGCs grow tree-like branches and respond to light stimulation (Venugopalan P et al. Nature Comm 2016. http://www.nature.com/articles/ncomms10472). In a Phase I trial testing ciliary neurotrophic factor (CNTF) in non-arteritic ischemic optic neuropathy and glaucoma, a semi-permeable membrane loaded with cells from a human retinal pigment epithelium (RPE) cell line that secreted CNTF was inserted into the vitreous. In 11 patients with various visual acuities, demographic characteristics and disease states, no serious adverse effects were seen while improvement was observed in some patients’ Humphrey visual field indices (VFI), including VFI and mean deviation, in one to three months, Dr Goldberg said. Retinal fibre layers also thickened significantly, though the benefit of this is uncertain. A larger controlled trial began recruiting in late 2016. Jeffrey Goldberg: smkohler@stanford.edu