Sunil K. Chauhan

Purpose: The aim of this study was to compare the rates of healing, scar formation, and regression of preexisting scars using topical murine hepatocyte growth factor (mHGF), recombinant human deleted HGF (dHGF), murine nerve growth factor (mNGF), and phosphate-buffered saline (PBS). Methods: Mechanical corneal epithelial and stromal injury was induced in C57BL/6 mice. Five groups of mice were studied in each of phase I (wound healing and scar formation) and phase II (regression of preexisting scars). Each group received topical 0.1% mHGF, 0.1% dHGF, 0.2% dHGF, 0.1% mNGF, or PBS. In phase I, animals were dosed 4 times/day (QID) on days 0 to 7. In phase II, a corneal injury was induced, and no treatment was administered for 10 days to allow scar formation. Mice with scars were then dosed QID on days 11 to 21. Ocular assessments included slit-lamp photography (phase I and II) and fluorescein staining (phase I). Results: In phase I, eyes treated with mHGF exhibited significantly faster epithelial healing and decreased scar formation compared with both mNGF-treated and PBS-treated eyes 7 days after treatment. Consistent with that seen in mHGF-treated eyes, 0.1% and 0.2% dHGF-treated eyes each showed significantly faster epithelial healing compared with PBS-treated eyes. Scars formed in dHGF-treated eyes were also significantly smaller than PBS-treated eyes 7 days after treatment. In phase II, both mHGF-treated and dHGF-treated eyes showed a significant decrease in the size of preexisting scars compared with PBS-treated eyes. Conclusions: Topical HGF significantly accelerates corneal wound healing, reduces scar formation, and can reverse preexisting scars.

Ocular surface inflammation and injury often lead to fibrosis and impaired vision. Myofibroblasts directly promote fibrosis by producing excessive extracellular matrix (ECM) proteins and alpha‐smooth muscle actin (ɑ‐SMA). In addition, macrophages have been shown to promote fibrosis by secreting pro‐fibrotic factors to stimulate myofibroblast formation. However, the capacity of macrophages to directly remodel ECM remains understudied. This study utilized a mouse model of corneal injury and fibrosis to determine whether macrophages transform into myofibroblast‐like cells during ocular surface inflammation. Following injury, F4/80 + ɑ‐SMA+ macrophages were present at the early stages of wound healing and increased in frequency and ɑ‐SMA intensity during the remodeling stage. The increase in F4/80 + ɑ‐SMA+ macrophages occurred due to the microenvironment transitioning from an inflammatory state to a pro‐fibrotic state. Activated human and mouse macrophages treated with pro‐fibrotic cytokines (IL‐10 and TGF‐β1) transitioned to ɑ‐SMA+ macrophages, adopting a spindle‐like phenotype and expressing signature myofibroblast ECM and cytoskeletal components, including ɑ‐SMA, desmin, fibronectin, and collagen III. Furthermore, gel contraction assays showed ɑ‐SMA+ macrophages significantly contracted a collagen gel, making them functionally resemble myofibroblasts. The results of this study indicate that macrophages have the capacity to transdifferentiate into myofibroblasts during ocular surface inflammation.

Different therapeutic modalities, including steroids, have been used to treat corneal scarring. However, the ability of steroids to reduce corneal scarring is limited and associated with numerous side effects. Our previous studies have demonstrated that topical hepatocyte growth factor (HGF) after corneal injury suppresses the development of stromal scars. Here, we investigated whether HGF can re-establish corneal clarity and normalize tissue structure in corneas with pre-existing scars. Corneal scarring was induced by mechanically removing the corneal epithelium and the anterior third of the stroma using a hand-held Algerbrush II in C57BL/6 mice. Substantial scar tissue formed by day 10 post-injury, at which time the epithelium was debrided and treated with 0.1% recombinant mouse HGF, 0.1% dexamethasone (steroid) or 0.1% control protein thrice a day for 10 days. Corneal clarity was significantly restored in the HGF treatment group, compared to both the steroid and control protein treatment groups. Moreover, HGF treatment downregulated the expression of αSMA and upregulated the expression of extracellular matrix-remodeling matrix metalloproteinases 1 and 10 (MMP1 and MMP10), suggesting HGF upregulates tissue remodeling molecule MMP1 and 10 to promote tissue restoration. These findings offer novel insights into the mechanisms by which HGF re-establishes corneal clarity, and promotes epithelial regeneration in corneas with pre-existing stromal scarring.

Mesenchymal stromal cells (MSCs) have been shown to modulate the function of various subsets of T cells such as naïve CD4 ⁺ T cells and IFNγ ⁺ CD4 ⁺ Th1 cells; however, mechanisms underlying this regulation have not been fully deciphered. Our in vitro culture assays demonstrate that MSCs suppress the activation and function of CD4 ⁺ T cells by secreting interleukin 11, and neutralization of IL11 abrogates MSC‐mediated suppression of CD4 ⁺ T cell function. Moreover, delayed‐type, exogenous supplementation of IL11 significantly suppressed IFNγ ⁺ expression by Th1 cells. Th1 and CD8 ⁺ cells play central roles in T cell‐mediated tissue damage. Using a murine model of hypersensitivity response to study T cell‐mediated tissue damage, we show that silencing IL11 in MSCs significantly abates the capacity of MSCs to suppress the generation of IFNγ‐secreting CD4 ⁺ and CD8 ⁺ cells, failing to prevent T cell‐mediated tissue inflammation and tissue damage.

Purpose: Regulation of inflammation is critical for achieving favorable outcomes in wound healing. In this study, we determine the functional role and mechanism of action of IL-11, an immunomodulatory cytokine, in regulating inflammatory response at the ocular surface. Methods: Corneal injury was induced by mechanical removal of the epithelium and anterior stroma using an AlgerBrush II. Transcript and protein levels of IL-11 in injured cornea were quantified using real-time PCR and ELISA analysis. Corneal inflammation was assessed by measuring frequencies of total CD45⁺ inflammatory cells, CD11b⁺Ly6G⁺ polymorphonuclear cells (neutrophils), and CD11b⁺Ly6G⁻ mononuclear cells (macrophages, monocytes) at the ocular surface using flow cytometry. To assess the effect of IL-11 on innate immune cell function, cell activation marker and inflammatory cytokines including major histocompatibility complex (MHC) class II, myeloperoxidase (MPO), TNFα, and inducible nitric oxide synthase (iNOS) were measured following recombinant IL-11 treatment (1 µg/mL). Injured corneas were topically treated with IL-11 (1 µg/mL), and wound healing was evaluated using corneal fluorescein staining. Results: Corneal injury resulted in increased levels of IL-11 in the cornea, particularly in the stroma. Neutrophils and CD11b⁺ mononuclear cells (macrophages, monocytes) substantially expressed IL-11 receptor. Interestingly, IL-11 significantly downregulated the activation of immune cells, as evidenced by the lower expression of MHC II and TNFα by CD11b⁺ mononuclear cells and lower levels of MPO by neutrophils. Topical administration of IL-11 to injured corneas led to faster wound healing and better retention of tissue architecture. Conclusions: Our findings demonstrate IL-11 is a key modulator of ocular surface inflammation and provide novel evidence of IL-11 as a potential therapeutic to control inflammatory damage and accelerate wound repair following injury.

The Anaesthesiology Department at Sawai Man Singh Medical College carried out this study. For this, 60 ASA grade I and II patients undergoing planned general surgery were randomly assigned into two groups of 30 each, with Group KP (n=30) receiving injections of ketamine at 0.3 mg/kg and Group MP receiving injections of midozolam at 0.03 mg/kg and Propofol I.V. The main goal of the study was to find the best induction by analysing changes in hemodynamic indicators from baseline to various time points after induction. On the basis of the necessary induction dose and hemodynamic characteristics, the groups were contrasted. The strategy used was to present the categorical data as percentages and compare them between groups using the Chi square test. The mean and standard deviation of the quantitative data were displayed, and students' t-tests were used to compare them. According to the study described above, group MP saw a greater fluctuation in heart rate than did group KP, whose heart rate remained more constant during the anaesthetic time. Group MP's blood pressure dropped more quickly after induction compared to group KP. The ketamine group's blood pressure remained the most stable out of all the groups. Apnea, pain upon injection, and uncontrollable movements were absent in the KP group. Of all the groups, the ketamine-propofol group required the least induction dose. As a result, we came to the conclusion that pretreatment with ketamine at a dose of 0.3 mg/kg results in better hemodynamic stability and requires less propofol for induction than midazolam does. The ketamine-propofol group is therefore the best of the two groups, making it the optimum induction agent

The Anaesthesiology Department at Sawai Man Singh Medical College carried out this study. For this, 60 ASA grade I and II patients undergoing planned general surgery were randomly assigned into two groups of 30 each, with Group KP (n=30) receiving injections of ketamine at 0.3 mg/kg and Group MP receiving injections of midozolam at 0.03 mg/kg and Propofol I.V. The main goal of the study was to find the best induction by analysing changes in hemodynamic indicators from baseline to various time points after induction. On the basis of the necessary induction dose and hemodynamic characteristics, the groups were contrasted. The strategy used was to present the categorical data as percentages and compare them between groups using the Chi square test. The mean and standard deviation of the quantitative data were displayed, and students' t-tests were used to compare them. According to the study described above, group MP saw a greater fluctuation in heart rate than did group KP, whose heart rate remained more constant during the anaesthetic time. Group MP's blood pressure dropped more quickly after induction compared to group KP. The ketamine group's blood pressure remained the most stable out of all the groups. Apnea, pain upon injection, and uncontrollable movements were absent in the KP group. Of all the groups, the ketamine-propofol group required the least induction dose. As a result, we came to the conclusion that pretreatment with ketamine at a dose of 0.3 mg/kg results in better hemodynamic stability and requires less propofol for induction than midazolam does. The ketamine-propofol group is therefore the best of the two groups, making it the optimum induction agent