Thymosin β4 (Tβ4) in eye and skin therapy: a dual-action peptide that promotes healing, inflammation control and hair regeneration

Description of the potential effects of the substance Thymosin β4 (Tβ4) Based on the literature. (This is not a product description, disclaimer at the bottom of the page)

Thymosin β4 in eye and skin therapy improves corneal healing and inflammation control

Thymosin β4 accelerates corneal healing and reduces abnormal blood vessel growth after chemical burns. Zhang et al. (2017) tested different eye treatments in rabbits with chemical corneal burns [1]. For 14 days, they compared normal saline solution, Gly-Tβ4 solution, gel without active ingredient, and Gly-Tβ4 in gel. The Gly-Tβ4 solution worked best, reducing corneal damage, inhibiting abnormal blood vessel growth and accelerating healing of the outer layer of the eye. In contrast, the Gly-Tβ4 gel caused minor irritation and seemed less effective, probably because it slowed the release of the drug. These results confirm that thymosin β4 solution is a promising agent for reducing damage and promoting healing after corneal burns. In addition, thymosin β4 helps the cornea heal faster and reduces inflammation after injury. In mice with chemically damaged corneas, Sosne et al (2002) used thymosin β4 eye drops twice daily [2]. The treated eyes healed faster and had fewer immune cells (white blood cells) in the area of injury. Laboratory tests showed lower levels of inflammatory molecules such as IL-1β and chemokines such as MIP-1α, MIP-1β, MIP-2 and MCP-1. This suggests that it not only speeds up healing, but also reduces the body's inflammatory response to injury (Sosne et al., 2002).

In addition, thymosin β4 drops help patients with severe corneal ulcers, but not in all types. Dunn et al (2010) used thymosin β4 eye drops without preservatives in nine patients with long-standing corneal ulcers of the " " type [3]. Within 4-7 weeks, six patients with large epithelial ulcers showed marked healing and no significant hypertrophy of blood vessels in the cornea. One patient had some corneal thinning. However, no significant improvement was observed in three patients with milder punctate defects. Nevertheless, all participants experienced symptom relief, such as a reduction in ocular irritation, soon after starting treatment. The results are consistent with previous laboratory studies showing that Tβ4 promotes cell migration and reduces inflammation. In another study, recombinant thymosin β4 eye drops improved tear production and reduced inflammation in autoimmune dry eye. Zhao et al (2023) treated rabbits with Sjögren's syndrome-like eye disease with recombinant thymosin β4 eye drops daily for four weeks [4]. The treatment improved tear secretion, stabilized the tear film and reduced damage to the ocular surface. In the tear glands, it reduced the levels of genes and proteins associated with inflammation, such as IL-17A, IL-17F, GM-CSF, and decreased the activation of a signaling molecule called STAT3. When the researchers tried to block this effect with another drug, the benefits of thymosin β4 were partially reversed, showing that it works through the STAT3 pathway to reduce inflammation.

In addition, thymosin β4 alleviates dry eye syndrome symptoms more effectively than common treatments in a dry environment model. Sosne et al (2015) tested different concentrations of thymosin β4 in a mouse model designed to simulate dry eye syndrome caused by stress and medication [5]. It significantly improved the ocular surface and outperformed standard treatments such as doxycycline and Restasis® (cyclosporine). The best results were obtained at 0.1% and 0.5% when applied twice daily. This demonstrates the strong protective and anti-inflammatory effects of thymosin β4 under conditions that mimic dry eye disease in humans (Sosne et al., 2015). In addition, thymosin β4 and dexamethasone restore the healing process after smoke exposure by repairing cell movement pathways. Yuan et al (2010) investigated how cigarette smoke affects the cornea's ability to heal [6]. When corneal tissue was exposed to secondhand smoke, it showed poor cell migration, disruption of the internal cell structure (actin cytoskeleton) and lower activity of proteins such as FAK, paxillin and RhoA, which are essential for proper wound healing. Using thymosin β4 alone slightly improved healing, but when combined with the anti-inflammatory drug dexamethasone, the healing defects were completely reversed. This combination restored normal cell movement and signaling activity, while overcoming the blockade of healing associated with inflammation. Therefore, it works best in combination with an anti-inflammatory drug to fully restore the healing ability of smoke-damaged eyes.

Moreover, thymosin β4 drops work as well or better than other dry eye syndrome treatments. In a mouse model of dry eye syndrome caused by dryness and drugs, Kim et al (2018) tested RGN-259 (thymosin β4-based eye drops) against three common treatments: cyclosporin A (CsA), dicvafosol em (DQS) and lifitegrast (LFA) [7]. RGN-259 restored tear production, as did DQS and LFA, and improved ocular surface smoothness, as did LFA; both results were unattainable with CsA. It also reduced surface cell detachment, similar to DQS and LFA, while CsA remained ineffective. For cup cells and mucin (important for healthy tears), RGN-259 worked as well as CsA, while the other two agents had no effect. In addition, RGN-259 reduced inflammatory markers similarly to CsA and LFA. In conclusion, RGN-259 appears to be a potent, multidirectional treatment for dry eye, promoting tear production, protecting the ocular surface, restoring mucus-secreting cells and reducing inflammation. 

It is worth noting that in their review, Sosne et al (2016) assessed the limitations of existing treatments for ocular surface disease, such as artificial tears, steroid drops and cyclosporine, which can relieve symptoms or reduce inflammation, but do not actively promote tissue healing [8]. They pointed to thymosin β4 as a natural peptide that not only helps repair damaged eye tissues, but also relieves inflammation. It promotes healthy cell movement and tissue closure, while controlling immune responses, making it a potential treatment for conditions such as dry eye syndrome, eyelid inflammation and nerve-related corneal problems. In another study, Sosne et al (2007) reviewed laboratory studies and animal models that showed that thymosin β4 reliably accelerates healing after corneal injury [9]. It encourages cells to move and close wounds while reducing inflammatory responses, especially those associated with NF-κB, a key molecule in the inflammatory process. It also prevents unnecessary cell death (anti-apoptotic action). This balanced action, promoting rapid healing without increasing risk, may be a safer alternative to steroids, which can slow healing or cause side effects. It may therefore be useful in treating corneal injuries and other problems related to the surface of the eye.

Thymosin β4 in eye and skin therapy promotes hair growth and skin regeneration.

Activates hair follicle stem cells and promotes hair growth. Philp et al. (2004) found that thymosin β4 helps initiate new hair growth by activating stem cells in a specific part of the hair follicle called the "bulge" [10]. In both rats and mice, as well as in hair follicle cells cultured in the laboratory, it increased stem cell migration and early-stage development. It also increased levels of MMP-2, a protein that helps remodel the area around hair follicles (the extracellular matrix), making it easier for cells to move and grow. These actions helped bring the hair cycle into the active growth phase, known as anagen. Interestingly, thymosin β4 works similarly or better than minoxidil in stimulating hair growth and stem cell movement. In an additional study, Philp et al. (2007) applied thymosin β4 topically to the skin of mice and rats and found that it induced faster hair regrowth than minoxidil [11]. Rats treated with Tβ4 had a higher percentage of active hair follicles (68.3%) compared to both the untreated group (56.0%) and the minoxidil-treated group (56.9%) ( ). In genetically modified mice that produced additional thymosin β4, hair grew back faster than in normal individuals from the same litter. In laboratory experiments, even at very low doses, it doubled the movement of stem cells from the bulge to the base of the hair follicle. It also induced the appropriate proteins (such as MMP-2) needed to remodel the tissue and promote early hair formation without increasing proteins such as MMP-9, which are not involved in hair follicle remodeling.

In addition, thymosin β4 in the skin accelerates hair regrowth and activates growth signals. Gao et al (2015) showed that mice with extra thymosin β4 in the skin grew back hair faster and produced more hair stalks that clustered together [12]. These mice also had higher levels of VEGF (vascular growth factor) and activated proteins such as p38, ERK and AKT, which promote hair growth. In contrast, mice without thymosin β4 grew hair more slowly and had fewer hair follicles. These results suggest that thymosin β4 activates VEGF and several cell growth pathways that stimulate hair production, while loss of thymosin β4 blocks this process. In addition, thymosin β4 activates the Wnt and VEGF pathways, promoting hair regrowth and matrix remodeling. In an additional study, Gao et al. (2016) examined the specific signals affected by thymosin β4 [13]. They found that important growth signals such as β-catenin, Lef1 (Wnt pathway), VEGF and MMP-2 were increased in mice with excess thymosin β4. These help form new blood vessels and remodel the matrix around hair follicles, promoting hair growth. The same markers were reduced in mice with the thymosin β4 gene turned off, but E-cadherin (a cell adhesion molecule) remained at the same level. This indicates that thymosin β4 specifically supports pro-growth pathways, rather than general cell binding, to promote hair follicle function.

In addition, thymosin β4 helps initiate the hair growth cycle and increases the number of hair follicles. According to a review by Dai et al. (2021), both the natural and the added form of thymosin β4 help start a new hair growth cycle [14]. It helps hair follicle stem cells to move and mature into hair-producing cells. In mice, it accelerates the rate of hair growth. In animals such as cashmere goats, it increases the number of secondary hair follicles, leading to greater cashmere production. Most of its action is related to improved cell movement, early cell development and communication with the dermal papilla (a key part of the hair follicle). In addition, thymosin β4 accelerates skin healing and may promote hair growth. In a scientific study, Philp et al. (2004) tested thymosin β4 on older mice (approximately 26 months old) with skin wounds [15]. When applied directly to the wounds, healing was faster and more collagen and repair tissue was formed. Skin cells moved faster from the edges, and wounds closed faster compared to untreated mice. These effects were observed not only with full-length thymosin β4, but also with a smaller fragment of the molecule consisting of 7 amino acids, which can still bind actin, which helps cells move. The researchers also noted that it may promote the formation of new hair follicles during this healing process, although this was based on observations rather than direct tests.

Applications

All available evidence indicates that thymosin β4 is a potent healing and anti-inflammatory compound. It helps cells move properly and rebuilds protective barriers while relieving harmful inflammation. In the eye, especially when used in liquid form, it improves both symptoms and clinical signs in laboratory and early human studies. It may work as well or even better than current dry eye medications, and in cases of severe inflammation, it has shown even greater efficacy when combined with steroids. To make further progress, researchers need to find the best dose, form of administration (liquid vs. gel) and time of administration, for both sudden trauma and long-term eye conditions. They also need to standardize how to measure the effectiveness of the treatment, including eye staining, tear quality, symptom relief and the health of mucus-producing cup cells, to fully demonstrate both its therapeutic and anti-inflammatory effects.

In skin and hair studies, thymosin β4's ability to activate stem cells, repair damaged support structures and trigger growth signals gives it great potential as a treatment for hair loss and poor skin healing. It has already shown promising results in animal studies compared to minoxidil. Future studies should focus on its long-term safety, the effect of different doses on outcomes (including the possibility that too high a dose may weaken the effect), and its efficacy in combination with other treatments, such as anti-inflammatory drugs or growth factor stimulants. If these studies continue to show positive results, it could become a valuable therapeutic option for both eye and skin care; a single, gentle therapy that promotes tissue repair and reduces inflammation in conditions such as dry eye syndrome, corneal damage, skin wounds and thinning hair.

Disclaimer

This article was written for educational purposes and is intended to raise awareness of the substance under discussion. It is important to note that the article is about the substance in general - it is not a description of a specific product (chemical reagent). We do not suggest using chemical reagents on humans - this is prohibited by law. For a product to be used for treatment, it must be registered as a drug. The information in the text is based on available scientific research and is not intended to serve as medical advice or promote self-medication. The reader should consult any health and treatment decisions with a qualified health professional.

References

1. Zhang, W., Nie, L., Du, L., Chen, W., Wu, Z., and Jin, Y. (2017). Topical treatment of corneal alkali burns with Gly-thymosin β4 solutions and in situ hydrogels by inhibiting corneal neovascularization and improving corneal epidermal regeneration in guinea pigs. Burns, 43(8), 1742-1747. https://doi.org/10.1016/j.burns.2017.05.002https://pubmed.ncbi.nlm.nih.gov/28602595/ 
2. Sosne, G., Szliter, E. A., Barrett, R., Kernacki, K. A., Kleinman, H., and Hazlett, L. D. (2002). Thymosin beta 4 promotes corneal wound healing and reduces inflammation in vivo after alkali injury. Experimental Eye Research, 74(2), 293-299. https://doi.org/10.1006/exer.2001.1125https://pubmed.ncbi.nlm.nih.gov/11950239/ 
3. Dunn, S. P., Heidemann, D. G., Chow, C. Y. C., Crockford, D., Turjman, N., Angel, J., Allan, C. B., and Sosne, G. (2010). Treatment of chronic non-healing neurotrophic corneal epithelial defects with thymosin beta 4. Annals of the New York Academy of Sciences, 1194, 199-206.https://doi.org/10.1111/j.1749-6632.2010.05471.xhttps://pubmed.ncbi.nlm.nih.gov/20536469/ 
4. Zhao, X., Li, N., Yang, N., Mi, B., Dang, W., Sun, D., Ma, S., Nian, H. and Wei, R. (2023). Thymosin β4 attenuates autoimmune inflammation of the lacrimal gland by inhibiting Th17 cell responses. Investigative Ophthalmology & Visual Science, 64(11), 3. https://doi.org/10.1167/iovs.64.11.3 https://pubmed.ncbi.nlm.nih.gov/37531112/
5. Sosne, G., Kim, C., and Kleinman, H. K. (2015). Thymosin β4 significantly reduces dryness symptoms in a mouse model of experimental dry eye syndrome in a controlled adverse environment. Expert Opinion on Biological Therapy, 15(Suppl 1), S155-S161. https://doi.org/10.1517/14712598.2015.1019858 https://pubmed.ncbi.nlm.nih.gov/26096547/
6. Yuan, H., Ma, C., Moinet, L., Sato, N., and Martins-Green, M. (2010). Reversal of corneal wound healing disorders induced by passive cigarette smoking by combining thymosin beta4 with anti-inflammatory agents. Investigative Ophthalmology & Visual Science., 51(5), 2424-2435. https://doi.org/10.1167/iovs.09-3692https://pubmed.ncbi.nlm.nih.gov/20019366/
7. Kim, C. E., Kleinman, H. K., Sosne, G., Ousler, G. W., Kim, K., Kang, S., Yang, J. (2018). RGN-259 (thymosin β4) improves the treatment of clinically significant dry eye syndrome compared with prescription drugs in a dry eye syndrome model. Scientific Reports, 8(1), 10500. https://doi.org/10.1038/s41598-018-28861-5 https://pubmed.ncbi.nlm.nih.gov/30002412/ 
8. Sosne, G., Rimmer, D., Kleinman, H. K., and Ousler, G. (2016). Thymosin beta 4: a potential new therapy for neurotrophic keratopathy, dry eye syndrome and ocular surface diseases. Vitamins and hormones, 102, 277-306. https://doi.org/10.1016/bs.vh.2016.04.012 https://pubmed.ncbi.nlm.nih.gov/27450739/
9. Sosne, G., Qiu, P. and Kurpakus-Wheater, M. (2007). Thymosin beta-4 and the eye: now I can see clearly, the pain is gone. Annals of the New York Academy of Sciences, 1112, 114-122. https://doi.org/10.1196/annals.1415.004
10. Philp, D., Nguyen, M., Scheremeta, B., St-Surin, S., Villa, A. M., Orgel, A., Kleinman, H. K., and Elkin, M. (2004). Thymosin beta4 increases hair growth through activation of hair follicle stem cells. FASEB Journal, 18(2), 385-387. https://doi.org/10.1096/fj.03-0244fje https://pubmed.ncbi.nlm.nih.gov/14657002/
11. Philp, D., St-Surin, S., Cha, H.-J., Moon, H.-S., Kleinman, H. K., and Elkin, M. (2007). Thymosin β4 induces hair growth through stem cell migration and differentiation. Annals of the New York Academy of Sciences, 1112, 95–103. https://doi.org/10.1196/annals.1415.009 https://pismin.com/10.1196/annals.1415.009 
12. Gao, X., Liang, H., Hou, F., Zhang, Z., Nuo, M., Guo, X., and Liu, D. (2015). Thymosin beta-4 induces hair growth in mice. PLoS ONE, 10(6), e0130040. https://doi.org/10.1371/journal.pone.0130040 https://pubmed.ncbi.nlm.nih.gov/26083021/
13. Gao, X.-Y., Hou, F., Zhang, Z.-P., Nuo, M.-T., Liang, H., Cang, M., Wang, Z.-G., Wang, X., Xu, T., Yan, L.-Y., Guo, X.-D. and Liu, D.-J. (2016). The role of thymosin beta 4 in hair growth. Molecular Genetics and Genomics, 291(4), 1639-1646. https://doi.org/10.1007/s00438-016-1207-y https://pubmed.ncbi.nlm.nih.gov/27130465/
14. Dai, B., Sha, R.-N., Yuan, J.-L. and Liu, D.-J. (2021). Multiple potential roles of thymosin β4 in hair follicle growth and development. Journal of Cellular and Molecular Medicine, 25(3), 1350-1358. https://doi.org/10.1111/jcmm.16241 https://pubmed.ncbi.nlm.nih.gov/33393222/
15. Philp, D., Goldstein, A. L., and Kleinman, H. K. (2004). Thymosin β4 promotes angiogenesis, wound healing and hair follicle development. Mechanisms of Ageing and Development, 125(2), 113–115. https://doi.org/10.1016/j.mad.2003.11.005 https://pismin.com/10.1016/j.mad.2003.11.005