Hippo Signaling Transduction Pathway Deregulation in Eye Diseases.

Introduction: Among the signaling pathways that regulate critical cell and tissue functions, the Hippo pathway is of great significance and under continuous investigation. The Hippo is a highly conversed pathway initially observed and decoded in Drosophila melanogaster. It consists of core molecules such as mammalian STE20-like kinase 1/2 (MST1/2), protein Salvador homologue 1 (SAV1) and MOBKL1A/B (MOB1A/B), and large tumour suppressor kinase 1/2 (LATS1/2), whereas the Yes-associated protein 1 (YAP), and WW-domain-containing transcription regulator 1 (TAZ) proteins act as transcriptional coactivators that bind to the transcriptional enhanced associated domain family 1(TEAD-1). Objective: The purpose of the current molecular review was to describe the main molecular and functional aspects of the Hippo pathway and its deregulation in specific eye lesions. Material and method: A systematic review of the literature was carried out based on the international medical database PubMed. The year 2005 was set as a prominent time limit for the publication date of the majority of articles, whereas specific references of great importance and historical value in the field of the Hippo discovery and analysis were also included. The following keywords were used: Hippo, TAZ, LATS, YAP1, eye, signaling pathway. A pool of 70 important articles was selected for the present review describing the connections between the implicated in HIPPO pathway molecules, the corresponding normal biochemical and functional features of them, and the deregulation mechanisms that are involved in the pathogenesis of eye lesions. Results: According to the selected publications, Hippo deregulation is observed in a broad spectrum of benign and neoplastic eye diseases. TAZ, LATS, and YAP1 proteins are negatively influenced by the deregulation of the core molecules in them. Conclusions: Hippo deregulation is critically involved in retina- and lens-related benign lesions as well as in conjunctival fibrosis and ocular surface squamous neoplasia. YAP/TEAD point mutations and abnormal expression of other molecules are the main genetic mechanisms in these lesions.