{"doi":"10.1167/iovs.64.11.7","title":"Effects of Cathepsin S Inhibition in the Age-Related Dry Eye Phenotype","abstract":"Purpose: Aged C57BL/6J (B6) mice have increased levels of cathepsin S, and aged cathepsin S (Ctss-/-) knockout mice are resistant to age-related dry eye. This study investigated the effects of cathepsin S inhibition on age-related dry eye disease. Methods: Female B6 mice aged 15.5 to 17 months were randomized to receive a medicated diet formulated by mixing the RO5461111 cathepsin S inhibitor or a standard diet for at least 12 weeks. Cornea mechanosensitivity was measured with a Cochet-Bonnet esthesiometer. Ocular draining lymph nodes and lacrimal glands (LGs) were excised and prepared for histology or assayed by flow cytometry to quantify infiltrating immune cells. The inflammatory foci (>50 cells) were counted under a 10× microscope lens and quantified using the focus score. Goblet cell density was investigated in periodic acid-Schiff stained sections. Ctss-/- mice were compared to age-matched wild-type mice. Results: Aged mice subjected to cathepsin S inhibition or Ctss-/- mice showed improved conjunctival goblet cell density and cornea mechanosensitivity. There was no change in total LG focus score in the diet or Ctss-/- mice, but there was a lower frequency of CD4+IFN-γ+ cell infiltration in the LGs. Furthermore, aged Ctss-/- LGs had an increase in T central memory, higher numbers of CD19+B220-, and fewer CD19+B220+ cells than wild-type LGs. Conclusions: Our results indicate that therapies aimed at decreasing cathepsin S can ameliorate age-related dry eye disease with a highly beneficial impact on the ocular surface. Further studies are needed to investigate the role of cathepsin S during aging.","journal":"Investigative Ophthalmology & Visual Science","year":2023,"id":340053,"datarank":0.42498200160843247,"base_score":2.833213344056216,"endowment":2.833213344056216,"self_citation_contribution":0.42498200160843247,"citation_network_contribution":0.0,"self_endowment_contribution":0.42498200160843247,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9562,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":946255,"name":"Kaitlin K. Scholand","orcid":"0000-0001-7556-8950","position":1,"is_corresponding":false},{"id":328831,"name":"Claudia M. Trujillo‐Vargas","orcid":"0000-0001-8546-2666","position":2,"is_corresponding":false},{"id":1074058,"name":"Wolfgang Haap","orcid":"0000-0001-6845-2124","position":3,"is_corresponding":false},{"id":1074059,"name":"Tiago Santos‐Ferreira","orcid":"0000-0002-2065-6440","position":4,"is_corresponding":false},{"id":884353,"name":"Christoph Ullmer","orcid":"0000-0002-1044-6722","position":5,"is_corresponding":false},{"id":1041538,"name":"Zhiyuan Yu","orcid":"0000-0003-0785-9822","position":6,"is_corresponding":false},{"id":283912,"name":"Cintia S. de Paiva","orcid":"0000-0002-9057-5494","position":7,"is_corresponding":false},{"id":647820,"name":"Jeremías G. Galletti","orcid":"0000-0002-5118-2540","position":0,"is_corresponding":true}],"reference_count":76,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:10:49.535464Z","pmid":"37540176","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}