Background: Glaucoma is a progressive optic neuropathy causing visual impairment and Retinal Ganglionic Cells (RGCs) death gradually posing a need for neuroprotective strategies to minimize the loss of RGCs and visual field. It is recognized as a multifactorial disease, Intraocular Pressure (IOP) being the foremost risk factor. ROCK inhibitors have been probed for various possible indications, such as myocardial ischemia, hypertension, kidney diseases. Their role in neuroprotection and neuronal regeneration has been suggested to be of value in the treatment of neurological diseases, like spinal-cord injury, Alzheimer’s disease and multiple sclerosis but recently Rho-associated Kinase inhibitors have been recognized as potential antiglaucoma agents. Evidence Synthesis: Rho-Kinase is a serine/threonine kinase with a kinase domain which is constitutively active and is involved in the regulation of smooth muscle contraction and stress fibre formation. Two isoforms of Rho-Kinase, ROCK-I (ROCK .) and ROCK-II (ROCK .) have been identified. ROCK II plays a pathophysiological role in glaucoma and hence the inhibitors of ROCK may be beneficial to ameliorate the vision loss. These inhibitors decrease the intraocular pressure in the glaucomatous eye by increasing the aqueous humour outflow through the trabecular meshwork pathway. They also act as anti-scarring agents and hence prevent post-operative scarring after the glaucoma filtration surgery. Their major role involves axon regeneration by increasing the optic nerve blood flow which may be useful in treating the damaged optic neurons. These drugs act directly on the neurons in the central visual pathway, interrupting the RGC apoptosis and therefore serve as a novel pharmacological approach for glaucoma neuroprotection. Conclusion: Based on the results of high-throughput screening, several Rho kinase inhibitors have been designed and developed comprising of diverse scaffolds exhibiting Rho kinase inhibitory activity from micromolar to subnanomolar ranges. This diversity in the scaffolds with inhibitory potential against the kinase and their SAR development will be intricated in the present review. Ripasudil is the only Rho kinase inhibitor marketed to date for the treatment of glaucoma. Another ROCK inhibitor AR-13324 has recently passed the clinical trials whereas AMA0076, K115, PG324, Y39983 and RKI-983 are still under trials. In view of this, a detailed and updated account of ROCK II inhibitors as the next generation therapeutic agents for glaucoma will be discussed in this review.

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The neuroprotective agents are not considered suitable to be administered through the traditional topical or oral route. This complementary drug therapy requires a delivery system that could release the drug to the optic nerve in a sustained manner and also increase patient compliance and tolerability. This review summarizes the use of ROCK inhibitors that could prevent the damage to the optic nerve along with the reduction in IOP and novel drug delivery systems to increase the efficacy of the drugs.

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Myrsine africana L. (Family Myrsinaceae) commonly known as mirting, is an evergreen shrub found wildly in tropical Asia to Africa. The plant has been traditionally used to treat various diseases and extensively used in folk medicine. The reported literature reveals that there is no pharmacological activities carried out on the fruits of M. africana in order to validate its traditional claim. The aim of the present study is to evaluate the anti-inflammatory and analgesic activity of methanolic and hydro-alcoholic extracts of fruits of M. africana at a dose level of 100, 200 and 500 mg/kg. The safety of drug was evaluated by sub-acute toxicity study as per OECD guidelines. The anti-inflammatory activity was carried out by carrageenan induced paw edema model and analgesic activity was done by hot plate, tail flick and acetic acid induced writhing methods. The maximum per cent inhibition of paw edema was found to be 57% in hydro-alcoholic extract at a dose level of 500 mg/kg in carrageenan induced paw edema model as compared to the standard drug ibuprofen (74.6%). The average response time at the dose of 500 mg/kg in tail flick and hot plate models was found to be 6.6 ± 0.79 mins and 6.89 ± 0.17 mins (at 120 mins and 90 mins) respectively which is comparable with the standard drug. In acetic acid writhing test both the extracts showed significant reduction in writhes as compared to standard. The pharmacological activities were found to be dose dependent. The acute toxicity study confirmed the drug to be non-toxic and safe. So it has been observed that the fruit of M. africana has marked beneficial effects against centrally and peripherally inflammation models and can be used to treat various disorders associated with inflammation.