Turkiye Klinikleri Journal of Ophthalmology

.: REVIEW
Yaşa Bağlı Maküla Dejenerasyonunda Matriks Metalloproteinazlar ve Matriks Metalloproteinaz İnhibitörlerinin Rolü
THE ROLE OF THE MATRIX METALLOPROTEINASES AND TISSUE INHIBITORS OF METALLOPROTEINASES IN AGE-RELATED MACULAR DEGENERATION
Turgut YILMAZa, Mete GÜLERa
aGöz Hastalıkları AD, Fırat Üniversitesi Tıp Fakültesi, ELAZIĞ
Turkiye Klinikleri J Ophthalmol. 2007;16(2):122-6
Article Language: TR
Full Text
ÖZET
Yaşa bağlı maküla dejenerasyonu (YBMD), gelişmiş ülkelerde 60 yaşın üstünde en önemli görme kaybı nedenlerinden biridir. Hastalık genellikle iki tipe ayrılır. Kuru ya da eksudatif olmayan tipi hastaların yaklaşık %85'ini oluşturur ve druzen birikimi ve/veya retina pigment epitelinin hipo/hiperpigmentasyonu gibi düzensizlikler ile karakterizedir. Hastaların yaklaşık %15'ini oluşturan yaş veya eksudatif tipi ise hastalığın daha ileri bir formudur ve koroid neovaskülarizasyonu ve/veya seröz retina dekolmanı ile karakterizedir. Eksudatif form YBMD'ye bağlı oluşan ağır görme kayıplarının yaklaşık %80-90'ından sorumludur. Matriks metalloproteinazlar (MMP) salgılanmış veya membrana bağlı şekilde bulunan, yapılarında çinko olan bir endopeptidaz ailesidir. Enzimler başlangıçta amino terminallerinin proteolitik parçalanmasıyla aktif hale gelen inaktif proenzimler olarak bulunurlar. Matriks metalloproteinazların aktiviteleri matriks metalloproteinaz inhibitörleri (TIMP) ile sıkı bir şekilde kontrol edilir. Matriks metalloproteinazlar ve TIMP'lerin arasındaki denge ekstraselüler matriksin bütünlüğünü düzenler ve birçok fizyolojik olayda anahtar rol oynar (embriyonik gelişme, bağ dokusu şekillenmesi, yara iyileşmesi ve anjiyogenez). Yaşa bağlı maküla dejenerasyonunun sebebi şimdilik tam anlaşılamamıştır ve tedavi seçeneklerinin artmasına karşın tedavisi henüz sınırlıdır. Çalışmalar, MMP ve TIMP'ler arasındaki dengesizliğin YBMD patogenezinde rol oynayabileceğini ve seçici MMP inhibisyonunun YBMD tedavisinde yeni bir seçenek olabileceğini göstermektedir.

Anahtar Kelimeler: Matriks metalloproteinazlar; matriks metalloproteinaz inhibitörleri; maküla dejenerasyonu.
ABSTRACT
Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries over the age of 60. The disease is generally divided in two types. The dry or non-exudative type of disease makes up about 85% of the cases and is characterized by drusen accumulation and/or retinal pigment epithelial (RPE) irregularities that include hyperpigmentation or hypopigmentary changes. Wet or exudative type is an advanced form of AMD that makes up about 15% of cases and is characterized by choroidal neovascularization (CNV) and/or serous RPE detachments. This form of the disease accounts for about 80-90% of the blindness observed in patients with AMD. The matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that exist in both secreted and membrane bound forms. The enzymes are initially expressed as inactive pro-enzymes becoming activated by proteolytic cleavage of their amino termini. The activity of MMPs is tightly regulated by the tissue inhibitors of metalloproteinases (TIMPs). The balance between MMPs and TIMPs regulates the integrity of the extracellular matrix and thus plays a key role in several physiological processes (embryonic development, connective tissue remodeling, wound healing, and angiogenesis). The cause of AMD is still poorly understood, and available treatment options, although increasing, are still limited. Studies suggest that an imbalance of MMPs and their inhibitors may be involved in pathogenesis of AMD and selective MMP inhibition may be a novel way to treat patiens with CNV.

Keywords: Matrix metalloproteinases; tissue inhibitor of metalloproteinases; macular degeneration

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30.03.2014

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