The outer retina (OR) represents the outermost layer of the retina, where the crucial process of light detection and its conversion into electrical signals occurs. It comprises several cell types each playing a pivotal role in the normal functioning of the retina. The disruption of these cell types has been correlated with various diseases, including age-related macular degeneration (AMD) and Stargardt disease (SD). Cell-cell interactions have been established to be essential for the proper function of these cells, and dysregulation in these interactions has been linked to retinal diseases. Recent advancements in high-throughput sequencing technologies have empowered scientists to analyze the expression levels of different genes at a cellular level. In this study, we employed RNA-seq datasets to analyze the expression profiles of the cell types including endothelial cells, rod photoreceptors and retinal pigment epithelium(RPE) in the OR, aiming to identify highly expressed genes in this region. These identified genes were subsequently used to retrieve Protein-Protein Interactions (PPIs) from publicly available databases, generating a comprehensive PPI network to elucidate the intricate interactions occurring within the OR. Through this methodology, we identified highly interacting gene products, potentially serving as promising candidates for pharmaceutical studies, thereby facilitating the identification of optimal drug targets. Highly interactive genes were identified based on the interaction datasets which were generated according to the captured interactions from two well-known databases such as STRING and IntAct.In addition to that , PPIs for some the genes which were missing from the databases was captured by manual search through literature. By comprehensively examining the molecular landscape and protein interactions within the outer retina, this study enhances our understanding of the underlying mechanisms governing its function. These findings hold implications for future therapeutic interventions and drug development targeting retinal diseases.
Ricostruzione delle reti di comunicazione cellula-cellula nella retina esterna. La retina esterna (RE) costituisce lo strato più esterno della retina, dove avviene il cruciale processo di rilevamento della luce e la sua conversione in segnali elettrici. Essa comprende diversi tipi cellulari, ognuno dei quali svolge un ruolo fondamentale nel normale funzionamento della retina. La disfunzione di questi tipi cellulari è stata correlata a varie patologie, tra cui la degenerazione maculare legata all'età (AMD) e la malattia di Stargardt (SD). Le interazioni cellula-cellula sono state dimostrate essere essenziali per la corretta funzione di queste cellule, e la disregolazione di tali interazioni è stata collegata a malattie retiniche. I recenti progressi nelle tecnologie di sequenziamento hanno permesso agli scienziati di analizzare i livelli di espressione di diversi geni a livello cellulare. In questo studio, abbiamo utilizzato set di dati di RNA-seq per analizzare i profili di espressione dei tipi cellulari presenti nella retina esterna, tra cui le cellule endoteliali, i fotorecettori a bastoncello e l'epitelio pigmentato retinico (RPE), al fine di identificare geni altamente espressi in questa regione. I geni identificati sono stati successivamente utilizzati per ricavare le interazioni proteina-proteina (PPIs) da database pubblicamente disponibili, generando una rete PPI completa per chiarire le intricate interazioni che avvengono all'interno della RE. Attraverso questa metodologia, abbiamo identificato prodotti genici altamente interagenti, che potrebbero fungere da candidati promettenti per studi farmaceutici, agevolando così l'individuazione di obiettivi farmacologici ottimali. I geni altamente interattivi sono stati identificati in base ai set di dati di interazione generati secondo le interazioni acquisite da due database ben noti come STRING e IntAct. Inoltre, le interazioni proteina-proteina per alcuni geni mancanti nei database sono state ricavate mediante ricerca manuale attraverso la letteratura scientifica. Attraverso un esame completo del campo molecolare e delle interazioni proteiche all'interno della retina esterna, questo studio migliora la nostra comprensione dei meccanismi che ne governano la funzione. Queste scoperte hanno implicazioni per future terapie e lo sviluppo di farmaci mirati alle malattie retiniche.
Reconstruction of cell-cell communication networks in the outer retina
AHMADI, ALIREZA
2022/2023
Abstract
The outer retina (OR) represents the outermost layer of the retina, where the crucial process of light detection and its conversion into electrical signals occurs. It comprises several cell types each playing a pivotal role in the normal functioning of the retina. The disruption of these cell types has been correlated with various diseases, including age-related macular degeneration (AMD) and Stargardt disease (SD). Cell-cell interactions have been established to be essential for the proper function of these cells, and dysregulation in these interactions has been linked to retinal diseases. Recent advancements in high-throughput sequencing technologies have empowered scientists to analyze the expression levels of different genes at a cellular level. In this study, we employed RNA-seq datasets to analyze the expression profiles of the cell types including endothelial cells, rod photoreceptors and retinal pigment epithelium(RPE) in the OR, aiming to identify highly expressed genes in this region. These identified genes were subsequently used to retrieve Protein-Protein Interactions (PPIs) from publicly available databases, generating a comprehensive PPI network to elucidate the intricate interactions occurring within the OR. Through this methodology, we identified highly interacting gene products, potentially serving as promising candidates for pharmaceutical studies, thereby facilitating the identification of optimal drug targets. Highly interactive genes were identified based on the interaction datasets which were generated according to the captured interactions from two well-known databases such as STRING and IntAct.In addition to that , PPIs for some the genes which were missing from the databases was captured by manual search through literature. By comprehensively examining the molecular landscape and protein interactions within the outer retina, this study enhances our understanding of the underlying mechanisms governing its function. These findings hold implications for future therapeutic interventions and drug development targeting retinal diseases.È consentito all'utente scaricare e condividere i documenti disponibili a testo pieno in UNITESI UNIPV nel rispetto della licenza Creative Commons del tipo CC BY NC ND.
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https://hdl.handle.net/20.500.14239/16371