Glokom, hem hastalar hem de doktorlar için tedavisi zor olan kronik, multifaktöriyel, nörodejeneratif bir hastalıktır. Günümüzde glokom tedavi modalitelerinin göz içi basıncını düşürmede her olguda yeterlilik sağlayamaması ve yan etkileri nedeni ile sıklıkla tedaviye uyum güçlüğü yaşanması, glokom patogenezindeki farklı etki mekanizmalarına ve uygulama yollarına yönelime yol açmıştır. Çıkış direncini azaltmak için doğrudan trabeküler ağ örgüsü (TM)/Schlemm kanalı/geleneksel çıkış yolunu hedef alan birkaç yeni topikal damla bileşiği geliştirilmiştir. Bunlar arasında Rho kinaz inhibitörleri, nitrik oksit veren bileşikler, adenozin reseptör agonistleri ve yeni prostaglandin analogları bulunur. Uzun süreli göz içi basıncını düşürücü ilaç dağıtım sistemi sunan alternatif tedaviler geliştirilmeye devam etmektedir. Bunlar gen terapisi ve kök hücre stratejileri ile birlikte kendi kendine uygulama yükünü kolaylaştırabilen veya birkaç yıl boyunca ortadan kaldırabilen topikal uygulamaları içerir. Gen tedavisinde; hücre içi fonksiyonları modifiye etmek için vektörler aracılığı ile gen taşınması ile defektif genin düzeltilmesi ve hücre içi var olan fonksiyonları değiştirmek amaçlanmaktadır. Ek olarak, terapötiklerin aylar boyunca kontrollü, sabit durumlu bir şekilde verilmesini amaçlayan çeşitli yeni formülasyonlar ve cihazlar da geliştirilmektedir. Ayrıca glokom tarafından uyarılan nörodejeneratif olayları engelleme potansiyeline sahip olan çeşitli moleküller tespit edilmiştir. Bunlar arasında memantin, koenzim Q ve sitikolin öne çıkanlardır. Glokomun patofizyolojisinde bilinmeyenler aydınlatıldıkça gelecekte bu multifaktöriyel hastalığın tedavisinde daha etkili moleküller, daha kolay ilaç uygulama yöntemleri ve daha kişisel tedavi stratejileri yer alacaktır.
Anahtar Kelimeler: Glokom; Rho ilişkili kinazlar; genetik tedavi; nörokoruma
Glaucoma is a chronic, multifactorial, neurodegenerative disease that can be challenging to treat for both patients and physicians. A lack of deficient in reducing intraocular pressure and the difficulty in adapting to treatment due to side effects in every each case therefore current glaucoma treatment modalities have led to different mechanism of effects and administration routes in glaucoma pathogenesis. Several new topical drop compounds directly targeting the trabecular meshwork (TM)/Schlemm canal/conventional outflow pathway to reduce outflow resistance has been developed. These include Rho kinase inhibitors, nitric oxide donating compounds, adenosine receptor agonists and new prostaglandin analogues. Alternative therapies that offer longterm intraocular pressure lowering drug delivery system are moving forward in development. These include gene therapy and stem cell strategies, which could ease or eliminate the burden of topical drop self-administration for several years. In gene therapy, it is intended to modify the intracellular functions of the defective gene by gene transport via vectors to modify the intracellular functions. Additionally, a variety of novel formulations and devices are in development that aim for controlled, steady state delivery of therapeutics over periods of months. Besides this, several molecules have been identified which have the potential to inhibit neurodegenerative events induced by glaucoma. Memantine, coenzyme Q and citicolin are among the prominent ones. As the unknowns in the pathophysiology of glaucoma are elucidated, in the future, the treatment of this multifactorial disease will include more effective molecules, easier drug delivery methods and more personal treatment strategies.
Keywords: Glaucoma; Rho-associated kinases; genetic therapy; neuroprotection
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