Kislay Roy, Bhasker Sriramoju, Rupinder K. Kanwar, Jagat R. Kanwar
Abstract
Alkali burn is a frequently occurring ocular injury that resembles ocular inflammation caused by eye allergies, infection, and refractive surgeries.
We investigated the synergistic regenerative potential of dominant negative survivin mutant (SurR9-C84A) and histone deacetylase (HDAC) inhibitor trichostatin-A (TSA) against alkali burn and corneal haze using human keratocytes and rabbit alkali burn model (Female New Zealand white rabbits).
Combination of SurR9-C84A and TSA suppressed levels of transforming growth factor (TGF)-β, alpha smooth-muscle actin (α-SMA), fibronectin and HDAC1, leading to apoptosis in myofibroblast cells and, showed the potential to clear the corneal haze. An insult with 0.5 N NaOH for 1 min led to neutrophils infiltration and formation of large vacuoles in the stroma. Treatments with TSA and SurR9-C84A for 40 min led to improvement in the conjunctival and corneal tissue integrity, marked by an increase in clathrin, and claudin expressions. An increase in TGF-β and endogenous survivin confirmed wound healing and cell proliferation in rabbit cornea. The blood analysis revealed a substantial decrease in the RBC, WBC, platelets, or the hemoglobin content post alkali burn. The cytokine array analysis revealed that NaOH induced expressions of IL-1α and MMP-9, which were found to be significantly downregulated (1.8 and 11.5 fold respectively) by the combinatorial treatment of SurR9-C84A and TSA.
Our results confirmed that combination of SurR9-C84A with TSA worked in synergy to heal ocular injury and inflammations due to alkali burn and led to the regeneration of ocular tissue by increasing clathrin, claudin, survivin, and TGF-β and reversal of alkali burn by suppressing IL-1α and MMP-9 without inducing haze.
This research output has an Altmetric Attention Score of 9. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 24 July 2017.
All research outputs
#3,701,499
of 22,881,154 outputs
Outputs from Frontiers in Pharmacology
#1,601
of 16,169 outputs
Outputs of similar age
#68,073
of 365,664 outputs
Outputs of similar age from Frontiers in Pharmacology
#20
of 143 outputs
Altmetric has tracked 22,881,154 research outputs across all sources so far. Compared to these this one has done well and is in the 83rd percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 16,169 research outputs from this source. They receive a mean Attention Score of 4.9. This one has done particularly well, scoring higher than 90% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 365,664 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 81% of its contemporaries.
We're also able to compare this research output to 143 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 86% of its contemporaries.
