Wound Healing In Glaucoma

Author(s):  
Kimberly A. Mankiewicz ◽  
Leonard K. Seibold

The goal of wound healing in most surgeries is to bring the injured tissue back to its original state to prevent the wound from reopening. However, in glaucoma surgery, the goal is to have incomplete wound healing. Scar formation prevents the filtering mechanism and bleb from functioning properly, leading to poor pressure control and failure of the surgery. However, if there is too little wound healing, surgical failure may be marked by overfiltration and hypotony. Several modulators are currently used in conjunction with glaucoma surgery, and new targets are under investigation to improve our ability to control the healing process. Normal wound healing occurs in 3 phases: the inflammatory phase, the proliferative/repair phase, and the remodeling phase. In the inflammatory phase, blood cells and plasma proteins are released around the wound site. These proteins attract other wound healing factors, such as cytokines and growth factors. White blood cells are also recruited to the site, clearing out undesired cellular debris through phagocytosis. Additionally, platelet aggregation and fibrin clot formation occur. In the proliferative/repair phase, fibroblasts, crucial cells for tissue repair and scarring, begin reforming the extracellular matrix (ECM) and other components of connective tissue. Angiogenesis also occurs, and the wound begins to close. In the final phase, blood vessels are resorbed and fibroblasts disperse. Fibroblasts produce matrix metalloproteinases that, along with collagen and elastin, allowing for wound remodeling and scar formation. The modulators used in glaucoma surgery, as well as new agents in development, disrupt various aspects of this cycle. Use of topical corticosteroids in conjunction with filtering surgery is a routine part of postoperative management and has been for many decades. Corticosteroids blunt the wound healing response by altering the inflammatory phase through reducing the amount of inflammatory cells and cytokines that migrate to the wound site. Corticosteroids also prevent the complexing and conversion of inflammatory mediators, as well as reduce vascular permeability to limit mobility of wound healing factors to the wound site.

Author(s):  
Swathi Balaji ◽  
Abdul Q. Sheikh ◽  
Lee Morris ◽  
Foong Y. Lim ◽  
Timothy M. Crombleholme ◽  
...  

Chronic ulcers are a leading cause of morbidity in diabetic patients. Diabetes is associated with major changes in the wound microenvironment and disruption of normal wound healing process, characterized by a prolonged inflammatory phase with elevated levels of wound proteases and increased degradation of extracellular matrix (ECM) components [1]. This impedes wound healing due to a lack of provisional matrix, impaired recruitment and survival of endothelial (EC) and endothelial precursor (EPC) cells, and insufficient neovascularization, resulting in delayed healing. Therefore, strategies focused on restoring the diabetic wound microenvironment by decreasing ECM degradation and promoting neovascularization are promising for development of new therapies to treat chronic diabetic ulcers.


2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Anisyah Ridiandries ◽  
Joanne T Tan ◽  
Christina A Bursill

Introduction: Wound healing is a multistep process involving inflammation, proliferation and remodelling at the wound site. Macrophages are important in the inflammatory stage to remove debris, however excessive macrophage accumulation may prolong the inflammatory response leading to prolonged wound healing, excessive scar formation and loss of function at the injury site. In the wound healing process, the CC-chemokine class is involved in the recruitment of macrophages to the wound site. Inhibition of the CC-chemokine class to reduce macrophage infiltration may present as strategy to increase wound closure and reduce scar formation. Aim: To determine if broad spectrum CC-chemokine inhibitor, 35K, can improve wound healing by reducing the inflammatory response and preventing scar formation. Results: Two full-thickness wounds were created on the dorsum, one each side of the midline, of C57BL6 mice. Wounds were treated topically with PBS or 35K protein daily for 10 days. Wounds treated with 35K closed significantly faster than PBS treated wounds between days 4 - 6 (p<0.05) post-wounding. Laser Doppler measurements revealed 35K significantly increased blood flow at the early (day 3-4) and late stages (day 10) of wound repair. Ten days after wounding, collagen was significantly lower in the 35K treated wounds (25.3% p<0.05). There were also reductions in neovessels (CD31, 39%, p<0.001), arterioles (alpha actin, 48% p<0.01) and macrophages (CD68, 25%), as a percentage of wound area, in 35K treated wounds. In wound tissue collected on day 4 (early stage) post-wounding, 35K treatment had an inhibitory effect on CCL2 and CCL5 protein by 41% (p<0.05) and 36% (p<0.05) respectively, and were reduced by 22% and 66% (p<0.05) respectively at day 10 (late stage) wound healing. Consistent with this, mRNA levels of p65 also decreased in both day 4 (34%, p<0.05) and day 10 (62%, p<0.05) wounds treated with 35K. Conclusion: The CC-chemokine class appears to play a key role in wound repair as topical application of CC-chemokine inhibitor 35K promoted wound healing. This was likely to be via inhibition of inflammation and promotion of blood flow recovery in the early stages of wound repair, thereby resulting in less scar formation.


2020 ◽  
Vol 26 (36) ◽  
pp. 4551-4568
Author(s):  
Mohammad Kashif Iqubal ◽  
Sadaf Saleem ◽  
Ashif Iqubal ◽  
Aiswarya Chaudhuri ◽  
Faheem Hyder Pottoo ◽  
...  

A wound refers to the epithelial loss, accompanied by loss of muscle fibers collagen, nerves and bone instigated by surgery, trauma, frictions or by heat. Process of wound healing is a compounded activity of recovering the functional integrity of the damaged tissues. This process is mediated by various cytokines and growth factors usually liberated at the wound site. A plethora of herbal and synthetic drugs, as well as photodynamic therapy, is available to facilitate the process of wound healing. Generally, the systems used for the management of wounds tend to act through covering the ruptured site, reduce pain, inflammation, and prevent the invasion and growth of microorganisms. The available systems are, though, enough to meet these requirements, but the involvement of nanotechnology can ameliorate the performance of these protective coverings. In recent years, nano-based formulations have gained immense popularity among researchers for the wound healing process due to the enhanced benefits they offer over the conventional preparations. Hereupon, this review aims to cover the entire roadmap of wound healing, beginning from the molecular factors involved in the process, the various synthetic and herbal agents, and combination therapy available for the treatment and the current nano-based systems available for delivery through the topical route for wound healing.


2000 ◽  
Vol 113 (13) ◽  
pp. 2455-2462 ◽  
Author(s):  
B. Eckes ◽  
E. Colucci-Guyon ◽  
H. Smola ◽  
S. Nodder ◽  
C. Babinet ◽  
...  

It is generally assumed that the vimentin intermediate filament network present in most mesenchymally-derived cells is in part responsible for the strength and integrity of these cells, and necessary for any tissue movements that require the generation of significant tractional forces. Surprisingly, we have shown that transgenic KO mice deficient for vimentin are apparently able to undergo embryonic development absolutely normally and go onto develop into adulthood and breed without showing any obvious phenotype. However, fibroblasts derived from these mice are mechanically weak and severely disabled in their capacity to migrate and to contract a 3-D collagen network. To assess whether these functions are necessary for more challenging tissue movements such as those driving in vivo tissue repair processes, we have analysed wound healing ability in wild-type versus vimentin-deficient embryos and adult mice. Wounds in vimentin-deficient adult animals showed delayed migration of fibroblasts into the wound site and subsequently retarded contraction that correlated with a delayed appearance of myofibroblasts at the wound site. Wounds made to vimentin-deficient embryos also failed to heal during the 24 hour culture period it takes for wild-type embryos to fully heal an equivalent wound. By DiI marking the wound mesenchyme and following its fate during the healing process we showed that this impaired healing is almost entirely due to a failure of mesenchymal contraction at the embryonic wound site. These observations reveal an in vivo phenotype for the vimentin-deficient mouse, and challenge the dogma that key morphogenetic events occurring during development require generation of significant tractional forces by mesenchymal cells.


2015 ◽  
Vol 51 (2) ◽  
pp. 415-427 ◽  
Author(s):  
Juliana Neves Rodrigues Ract ◽  
Fabiana Andreia Schäfer De Martini Soares ◽  
Hosana Gomes Rodrigues ◽  
José Ricardo Bortolon ◽  
Gilson Masahiro Murata ◽  
...  

<p>Two oil blends (sunflower/canola oils 85/15 (BL1) and canola/linseed oils 70/30 (BL2)), were prepared and enzymatically interesterified to be applied to surgically-induced wounds in rats. Following surgery, the animals were submitted to the Treatment with Physiological Saline (TPS) (control group), Blends (TBL), and Structured Lipids (TSL). The control group (TPS) received physiological saline solution for 15 days. In TBL, BL1 was administered during the inflammation phase (days 0-3) and BL2 in the tissue formation and remodeling phase (days 4-15). In TSL, Structured Lipid 1 (SL1) and Structured Lipid 2 (SL2) were used instead of BL1 and BL2, respectively. The aim of this study was to compare wound closure evolution among rats treated with the blends or structured lipids versus control rats treated with physiological saline. The wound healing process was evaluated by measuring the wound areas along the treatments and the concentrations of cytokines. An increase in the areas of wounds treated with the blends and structured lipids in the inflammatory phase was observed, followed by a steeper closure curve compared to wounds treated with physiological saline. The changes observed during the inflammatory phase suggest a potential therapeutic application in cutaneous wound healing which should be further investigated.</p>


2018 ◽  
Vol 4 (2) ◽  
pp. 109
Author(s):  
Mufimah Mufimah ◽  
Uti Rusdian Hidayat ◽  
Ichsan Budiharto

Abstract: Efectiveness Gel Extract Of White On The Process Of Healing Inflamation Phase Heating. The inflammatory phase is a favorable body response as a protection mechanism. In the process of wound healing becomes a very important phase. Management of inflammation that is often used Non-Steroid Anti-Inflammatory class of salicylates on the skin that have side effects. The content of allicin in garlic can be used for problems that begin with the inflammatory phase. The use of gel from garlic extract is also easier to use and easier to clean. The study aim to determine the effectiveness of garlic extract gel to process wound inflammatory phase healing. This research is an experimental research with pre and post test with control group method with 24 samples. Conducted injury to the back area of rat length of wound 1 cm, depth to dermis. Conducted wound care, given gel extract of garlic concentration of 20%, 40%, 80% of the control using 0.9% NaCl compress. Using Kruskal Wallis test and Anova oneway showed concentration of 20%, 40%, and 80% of sig <0,05 ie 0.00. It was concluded that 20%, 40%, 80% garlic extract gel was effective against inflammatory wound healing process. The use of garlic extract gel is more effective in the wound inflammatory wound healing process.Abstrak: Efektivitas Gel Ekstrak Bawang Putih  terhadap Proses Penyembuhan Luka Fase Inflamasi.  Fase inflamasi merupakan respon tubuh yang menguntungkan sebagai mekanisme perlindungan. Pada proses penyembuhan luka menjadi fase yang sangat penting. Penatalaksanaan inflamasi yang sering digunakan Anti-Inflamasi Non Steroid golongan salisilat pada kulit yang memiliki efek samping. Kandungan zat allicin pada bawang putih dapat dimanfaatkan untuk masalah yang diawali dengan fase inflamasi. Pemanfaatan gel dari ekstrak bawang putih pun dalam penggunaannya lebih mudah diabsorsi dan mudah dibersihkan. Penelitian ini bertujuan untuk mengetahui efektifitas gel ekstrak bawang putih terhadap proses penyembuhan luka fase inflamasi. Penelitian ini merupakan penelitian eksperiment dengan metode pre and post test with control grup dengan jumlah sampel sebanyak 24 ekor tikus. Dilakukan perlukaan pada daerah punggung tikus panjang luka 1 cm, kedalaman sampai dermis. Dilakukan perawatan luka, diberi gel ekstrak bawang putih konsentrasi berbeda yaitu 20%, 40%, 80%  kontrol menggunakan kompres NaCl 0,9%. Hasil uji Kruskal Wallis dan Anova oneway menunjukkan konsentrasi 20%, 40%, dan 80%  nilai sig <0,05 yaitu 0,00. Disimpulkan bahwa 20%, 40%, 80% gel ekstrak bawang putih efektif terhadap proses penyembuhan luka inflamasi. Penggunaan gel ekstrak bawang putih lebih efektif dalam proses penyembuhan luka inflamasi luka.   Disimpulkan bahwa 20%, 40%, 80% gel ekstrak bawang putih efektif terhadap proses penyembuhan luka inflamasi. Penggunaan gel ekstrak bawang putih lebih efektif dalam proses penyembuhan luka inflamasi luka.


2019 ◽  
Vol 34 (8) ◽  
pp. 1171-1187
Author(s):  
Farnoush Oveissi ◽  
Naser Tavakoli ◽  
Mohsen Minaiyan ◽  
Mohammad Reza Mofid ◽  
Azade Taheri

Epidermal lipoxygenase enzyme extracted from Ambystoma mexicanum (AmbLOXe) is known to accelerate the wound-healing process. AmbLOXe as a protein suffers from inactivation and losing its activity during formulation. Therefore, a delivery system that protects AmbLOXe from inactivation and preserves its activity is needed. We prepared AmbLOXe-loaded pectin nanoparticles (AmbLOXe Pec-NPs) and placed them into an alginate hydrogel. AmbLOXe Pec-NPs incorporation into the alginate hydrogel provides a means for controlled and sustained delivery of AmbLOXe to the wound site. Furthermore, the suitable swelling behavior and mechanical properties of AmbLOXe Pec-NPs alginate hydrogel make it feasible for clinical use. AmbLOXe Pec-NPs alginate hydrogel significantly enhanced the wound-healing process on the rat full-thickness excisional wounds, increased the rate of wound closure, enhanced the re-epithelialization and decreased the incidence of abnormal scarring. AmbLOXe Pec-NPs alginate hydrogel can be proposed as an effective wound hydrogel for improving wound healing with minimal scarring.


Nanomaterials ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 1108
Author(s):  
Edorta Santos-Vizcaino ◽  
Aiala Salvador ◽  
Claudia Vairo ◽  
Manoli Igartua ◽  
Rosa Maria Hernandez ◽  
...  

Negatively charged microspheres (NCMs) represent a new therapeutic approach for wound healing since recent clinical trials have shown NCM efficacy in the recovery of hard-to-heal wounds that tend to stay in the inflammatory phase, unlocking the healing process. The aim of this study was to elucidate the NCM mechanism of action. NCMs were extracted from a commercial microsphere formulation (PolyHeal® Micro) and cytotoxicity, attachment, proliferation and viability assays were performed in keratinocytes and dermal fibroblasts, while macrophages were used for the phagocytosis and polarization assays. We demonstrated that cells tend to attach to the microsphere surface, and that NCMs are biocompatible and promote cell proliferation at specific concentrations (50 and 10 NCM/cell) by a minimum of 3 fold compared to the control group. Furthermore, NCM internalization by macrophages seemed to drive these cells to a noninflammatory condition, as demonstrated by the over-expression of CD206 and the under-expression of CD64, M2 and M1 markers, respectively. NCMs are an effective approach for reverting the chronic inflammatory state of stagnant wounds (such as diabetic wounds) and thus for improving wound healing.


Molecules ◽  
2020 ◽  
Vol 25 (15) ◽  
pp. 3401
Author(s):  
David Meléndez-Martínez ◽  
Luis Fernando Plenge-Tellechea ◽  
Ana Gatica-Colima ◽  
Martha Sandra Cruz-Pérez ◽  
José Manuel Aguilar-Yáñez ◽  
...  

Chronic wounds are a major health problem that cause millions of dollars in expenses every year. Among all the treatments used, active wound treatments such as enzymatic treatments represent a cheaper and specific option with a fast growth category in the market. In particular, bacterial and plant proteases have been employed due to their homology to human proteases, which drive the normal wound healing process. However, the use of these proteases has demonstrated results with low reproducibility. Therefore, alternative sources of proteases such as snake venom have been proposed. Here, we performed a functional mining of proteases from rattlesnakes (Crotalus ornatus, C. molossus nigrescens, C. scutulatus, and C. atrox) due to their high protease predominance and similarity to native proteases. To characterize Crotalus spp. Proteases, we performed different protease assays to measure and confirm the presence of metalloproteases and serine proteases, such as the universal protease assay and zymography, using several substrates such as gelatin, casein, hemoglobin, L-TAME, fibrinogen, and fibrin. We found that all our venom extracts degraded casein, gelatin, L-TAME, fibrinogen, and fibrin, but not hemoglobin. Crotalus ornatus and C. m. nigrescens extracts were the most proteolytic venoms among the samples. Particularly, C. ornatus predominantly possessed low molecular weight proteases (P-I metalloproteases). Our results demonstrated the presence of metalloproteases capable of degrading gelatin (a collagen derivative) and fibrin clots, whereas serine proteases were capable of degrading fibrinogen-generating fibrin clots, mimicking thrombin activity. Moreover, we demonstrated that Crotalus spp. are a valuable source of proteases that can aid chronic wound-healing treatments.


2018 ◽  
Vol 38 (2) ◽  
Author(s):  
Zhen-han Deng ◽  
Jian-jian Yin ◽  
Wei Luo ◽  
Ronak Naveenchandra Kotian ◽  
Shan-shan Gao ◽  
...  

Chronic nonhealing wounds pose a significant challenge to healthcare system because of its tremendous utilization of resources and time to heal. It has a well-deserved reputation for reducing the quality of life for those affected and represent a substantial economic burden to the healthcare system overall. Earthworms are used as a traditional Chinese medicine, and have been applied pharmacologically and clinically since a long time in China. However, there is paucity in data regarding its wound healing effects. Therefore, we investigated the effect of earthworm extract (EE) on skin wound healing process. The obtained data showed that EE has healing effects on local wound of mice. It decreased the wound healing time and reduced the ill-effects of inflammation as determined by macroscopic, histopathologic, hematologic, and immunohistochemistry parameters. The potential mechanism could be accelerated hydroxyproline and transforming growth factor-β secretion—thus increasing the synthesis of collagen, promoting blood capillary, and fibroblast proliferation. It could accelerate the removal of necrotic tissue and foreign bodies by speeding up the generation of interleukin-6, white blood cells, and platelets. It thus enhances immunity, reduces the risk of infection, and promotes wound healing. All in all, the obtained data demonstrated that EE improves quality of healing and could be used as a propitious wound healing agent.


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