| Glaucoma is the leading cause of irreversible blindness worldwide.The molecular etiology of glaucoma is complex and unclear.Currently,few drugs are available for glaucoma.In response to the above problems,the first part screened out drugs with strong correlation with glaucoma through data analysis.Based on glaucoma genes including genetic factors and differential expression(DE)genes,a systematic analysis of glaucoma candidate drugs / chemicals was performed.In total,401 genes from the genetic database and 1656 genes from the DE genetic analysis were included in further analysis.In terms of glaucoma-related genetic factors,54 pathways were significantly enriched(FDR <0.05),and 96 DE gene pathways were significantly enriched(FDR <0.05).Searching for diseases related to glaucoma-related genes in the Phe WAS database returned 1,289 diseases,and search for 1,356 diseases in DE-glaucoma-related genes.Cardiovascular diseases,neurodegenerative diseases,cancer and ophthalmic diseases are highly related to glaucoma genes.A search of the DGIdb,KEGG and CLUE databases revealed a set of drugs / chemicals targeting the glaucoma gene.An analysis of the candidate drug use and glaucoma on the electronic medical records(EMR)of 136,128 patients treated by the Sichuan Provincial People’s Hospital subsequently revealed 9 drug candidates.Of these drugs,the incidence of glaucoma is lowest in patients receiving nicardipine.Based on the information in the drug database,the 40 drug candidates most likely to be used for glaucoma treatment are highlighted.Based on these findings,we conclude that the molecular mechanism of glaucoma is complex and may be a reflection of systemic disease.A set of ready-to-use drug candidates for glaucoma genes can be developed for clinical treatment of glaucoma.Our results provide a systematic explanation of glaucoma genes,their interactions with other systemic diseases,and drug / chemical candidates.In the second part,in vitro and in vivo experiments were performed on the screened drugs Celecoxib,donepezil and aspirin.The main contents are:——To verify the effect of different drug concentrations on human trabecular meshwork cells by using means such as apoptosis and cell proliferation.As a result,it was found that celecoxib had an effect of reducing intraocular pressure after continuous administration of C57 mice.Subsequently,in vitro experiments on celecoxib showed that celecoxib was less cytotoxic.Based on these findings,we conclude that the molecular mechanism of glaucoma is complex and may be a reflection of systemic disease.Through a set of ready-to-use drug candidates for glaucoma genes,clinical treatment drugs for glaucoma can be developed.Our results provide a systematic explanation of glaucoma genes,their interactions with other systemic diseases,and candidate drugs / compounds. |
