James C. Tsai

Intravitreal Administration of Erythropoietin and Preservation of Retinal Ganglion Cells in an Experimental Rat Model of Glaucoma

Purpose: The aim of this pilot study was to evaluate the potential neuroprotective effect of an intravitreal injection of erythropoietin (EPO) on retinal ganglion cell (RGC) preservation in an episcleral vessel cautery–induced rat model of glaucoma. Methods: The animals were randomly assigned into an unoperated control group (n = 11) and three experimental groups: episcleral vessel cautery only (EVC: n = 4), episcleral vessel cautery with intravitreal normal saline injection (EVC-NS; n = 5), and episcleral vessel cautery with intravitreal EPO treatment (EVC-EPO; n = 9). The intravitreal injections were limited to 5 μl containing either normal saline alone or 200 ng of EPO in normal saline administered immediately after the cautery procedure. RGCs were labeled retrogradely by FluoroGold neuron tracer 5 to 7 days prior to the collection of eyes at day 21 and counted in whole flat-mounted retinas with fluorescence microscopy. Results: Compared to the RGC counts in retinal specimens from unoperated control rats (12,619 ± 310), the corresponding RGC counts were significantly decreased in both the EVC (9116 ± 273; p < 0.005) and EVC-NS (9489 ± 293; p < 0.005) groups but not significantly decreased in the EVC-EPO (11,212 ± 414; p = 0.051) treated retinas. Conclusions: A single intravitreal 200 ng dose of EPO appears to have a protective effect on RGC viability in an in vivo rat model of glaucoma. Further experimental studies are needed to confirm these preliminary results and to optimize the appropriate dose and frequency of EPO delivery in animal models of glaucoma.

Erythropoietin: a candidate neuroprotective agent in the treatment of glaucoma.

Glaucoma is a progressive optic neuropathy that is the leading cause of irreversible blindness in the world. Although methods to lower intraocular pressure are the mainstay of glaucoma therapy, there are currently no available treatment modalities targeted at neuroprotection. Erythropoietin is a hematopoietic cytokine that has been shown to possess remarkable tissue-protective properties in preclinical models of neurodegeneration. As a result, there is a growing interest to explore the neuroprotective properties of erythropoietin as a possible therapeutic agent in neuropathic diseases of the eye such as glaucoma. Initial results in animal models have been promising, but further studies are needed to fully evaluate the safety and efficacy of this candidate neuroprotective agent in clinical trials.

Current and emerging medical therapies for glaucoma

Glaucoma is a multifactorial optic neuropathy in which there is a characteristic acquired loss of retinal ganglion cells, at levels beyond normal age-related baseline loss, and corresponding atrophy of the optic nerve. Although asymptomatic in its earlier stages, the disease is nevertheless one of the leading global causes of irreversible blindness. Although elevated intraocular pressure (IOP) is one of the most important risk factors and lowering of IOP is the only proven treatment so far, the definition of glaucoma has evolved from a disease caused by increased IOP to one characterised by an IOP-sensitive, progressive optic neuropathy. In recent years, safer and better tolerated topical medications have been developed to control IOP more effectively, thereby limiting the need for surgery. New research has also noted the importance of diurnal IOP variation as a critical risk factor for progression of glaucomatous optic neuropathy (GON) and subsequent visual field loss. Moreover, new discoveries have further elucidated the basic pathophysiological and genetic mechanisms underlying the elevated levels of IOP, as well as the cellular mechanisms of GON. As our understanding of these complex pathways continues to improve, development opportunities for new therapeutic modalities will be enhanced.

Glaucoma medications: use and safety in the elderly population.

As with many diseases, glaucoma increases in frequency in older populations, and is very often encountered in patients taking multiple medications. While the exact mechanism of glaucomatous optic neuropathy (GON) is not known, intraocular pressure (IOP) is thought to be central to the process, and reducing IOP is the only known effective treatment. The newer definition of glaucoma is an IOP-sensitive optic neuropathy. While large, controlled studies have indicated that reducing IOP will slow the progression of disease, the contributions of other conditions and medications have not been adequately studied. As the adverse effect profiles of medical therapies for glaucoma have improved, use of these agents has increased greatly. This has resulted in a large number of older patients taking glaucoma medications. Since topical medications can easily be overlooked in a medical history, and are for the most part well tolerated, systemic complications from these agents can be missed. In addition to being a common disease requiring treatment, glaucoma is also a model system for other degenerative diseases, and many of the concepts originally developed in relation to neurodegenerative diseases such as Alzheimer’s disease are under investigation for glaucoma. These include approaches targeted towards neuroprotection and excitotoxicity.