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  • Introduction Glaucoma consists of a group of eye diseases

    2022-12-02

    Introduction Glaucoma consists of a group of eye diseases showing a broad spectrum of clinical presentation and unknown aetiologies, that lead to a permanent loss of visual function due to the death of retinal ganglion 5-Ethynyl-2'-deoxyuridine and damage of the optical nerve. It is well accepted that a critical risk factor in the pathogenesis of glaucoma is the elevation in intraocular pressure (IOP) and it is the only proven treatable risk factor. IOP is generated and maintained by the aqueous humor circulation system in the anterior eye. Elevated IOP occurs from an imbalance between production and outflow of aqueous humor. The aqueous humor is a transparent nutritional fluid that provides the nutrients to the inner avascular structures of the eye. The control of the aqueous humor production occurs in the ciliary body and it is regulated by the sympathetic nervous system. Noradrenaline released from the sympathetic terminals stimulate adrenergic receptors that facilitate the production of the aqueous humor. This fact has been taken by the pharmaceutical companies to develop a series of antagonists of mainly β2-adrenoceptors to reduce aqueous humor production, reducing IOP in glaucoma. Other drugs currently used to decrease the rate of aqueous humor inflow are carbonic anhydrase inhibitors and α1-adrenoceptor agonists. Additionally, there are pharmacological agents such as cholinoceptor agonists and prostaglandin analogs that lower IOP by increasing the rate of aqueous humor outflow. Thus, pharmacological reduction of IOP by decreasing the rate of aqueous humor inflow or increasing the rate of aqueous outflow is the current therapeutic approach for preserving visual function in glaucoma patients. However, all the pharmacological agents mentioned can have various undesirable effects. For instance, β2-adrenoceptors blockers can cause substantial cardiovascular and respiratory side effects, carbonic anhydrase inhibitors use must be restricted in subjects with renal disease and patients with compromised endothelium, prostaglandin analogs can originate conjunctival hyperaemia, lengthening and thickening of eyelashes or changes in eye color. Moreover, the efficacy of these drugs is also likely to be reduced after prolonged use. Thus, there is the need to discover novel agents from the presently available pharmacological classes. In this context, RNA interference-based therapy for glaucoma can be an attractive alternative approach. RNA interference involves specific gene expression silencing by small molecules of double stranded RNA: small interference RNAs (siRNAs). The eye is currently considered a good target for RNAi therapy mainly because it is an accessible and confined compartment. The accessibility of the eye facilitates siRNA delivery, and naked siRNAs have been efficiently applied by topical administration to the anterior segment or by intravitreal injection to the posterior segment. In addition, its confined location provides several advantages. Local delivery of compounds to the eye restricts systemic exposure and reduces the amount of compound needed diminishing potential side effects outside the eye. Moreover, the immune system has a limited access to the eye; therefore immune responses to the compound are less likely to occur. As the localized delivery of siRNA to the eye is less challenging than for other tissues, there has been significant progress made toward its use as a therapeutic procedure for eye diseases. In fact, several siRNA-based therapeutic agents for ocular disorders such as wet age-related macular degeneration and diabetic retinopathy have already reached clinical trials.
    Materials and methods
    Results
    Discussion Glaucoma is one of the leading causes of blindness in the world. Anti-glaucomatous drugs currently prescribed can have various undesirable effects and their efficacy is also subject to a reduction after prolonged use. Moreover, to maintain adequate levels of IOP, frequent instillation is necessary, which can lead to poor compliance of the patient. Therefore, the development of new therapeutic strategies to circumvent the drawbacks associated to the presently available pharmacologic classes is required. In this context, we analyzed siRNA-based therapy for glaucoma.