Literature Review: The Role of Adipose Stem Cell Secretome In Caspase-3 Regulation and Endothelial Cell Density Preservation in Corneal Regeneration Post-Phacoemulsification

Authors

  • Birgitta Henny Perwitasari
  • Evelyn Komaratih
  • Dicky Hermawan

DOI:

https://doi.org/10.63682/jns.v14i14S.4037

Keywords:

Phacoemulsification, corneal endothelial damage, endothelial cell density, caspase-3, adipose-derived stem cell secretome, New Zealand white rabbit

Abstract

Phacoemulsification is the most widely used surgical technique for cataract removal; however, it poses risks of corneal endothelial damage, leading to complications such as corneal edema and vision impairment. The corneal endothelium plays a crucial role in maintaining corneal transparency, yet it has limited regenerative capacity. Endothelial cell loss following phacoemulsification results from mechanical trauma, oxidative stress, and apoptosis, with caspase-3 acting as a key mediator of programmed cell death. Excessive apoptosis leads to a critical reduction in endothelial cell density (ECD), causing corneal decompensation and potential vision loss. Current treatments, including endothelial keratoplasty, are limited by donor shortages and surgical risks. Stem cell-derived secretomes, particularly from adipose-derived stem cells (ASCs), have emerged as a promising therapeutic approach for corneal endothelial repair. ASC secretomes contain bioactive molecules such as growth factors and cytokines that promote endothelial cell survival, reduce apoptosis by downregulating caspase-3, and enhance tissue regeneration. Preclinical studies suggest that ASC secretomes may effectively support endothelial recovery post-phacoemulsification. This literature review explores the mechanisms of endothelial damage, the role of apoptosis in corneal cell loss, and the therapeutic potential of ASC secretomes as a novel intervention for protecting and restoring corneal endothelium following cataract surgery. Additionally, the use of  New Zealand white rabbits as an animal model for studying endothelial regeneration is discussed.

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References

Chiang PPC, Lamoureux EL, Zheng Y, Tay WT, Mitchell P, Wang JJ, et al. Frequency and risk factors of non-retinopathy ocular conditions in people with diabetes: The Singapore Malay Eye Study. Diabet Med. 2013;30(2):32–40.

Jaggernath J, Gogate P, Moodley V, Naidoo KS. Comparison of cataract surgery techniques: Safety, efficacy, and cost-effectiveness. Eur J Ophthalmol. 2013;24(4):520–6.

Martínez MB, Moyano DB, González-Lezcano RA. Phacoemulsification: Proposals for improvement in its application. Healthc. 2021;9(11):1–13.

Zhang JH, Ramke J, Lee CN, Gordon I, Safi S, Lingham G, et al. A Systematic Review of Clinical Practice Guidelines for Cataract: Evidence to Support the Development of the WHO Package of Eye Care Interventions. Vis. 2022;6(2):1–23.

Feizi S. Corneal endothelial cell dysfunction: etiologies and management. Ther Adv Ophthalmol [Internet]. 2018;10:1–19. Available from: https://journals.sagepub.com/doi/10.1177/2515841418815802

Rouhbakhshzaeri M, Rabiee B, Azar N, Ghahari E, Putra I, Eslani M, et al. New ex vivo model of corneal endothelial phacoemulsification injury and rescue therapy with mesenchymal stromal cell secretome. J Cataract Refract Surg [Internet]. 2019;45(3):361–6. Available from: https://doi.org/10.1016/j.jcrs.2018.09.030

WHO. Decade of Healthy Ageing 2020-2030. World Heal Organ. 2019;1–27.

Khalid M, Ameen SS, Ayub N, Mehboob MA. Effects of anterior chamber depth and axial length on corneal endothelial cell density after phacoemulsification. Pakistan J Med Sci. 2019;35(1):200–4.

Fortingo N, Melnyk S, Sutton SH, Watsky MA, Bollag WB. Innate Immune System Activation, Inflammation and Corneal Wound Healing. Int J Mol Sci. 2022;23(23).

De Saint Jean A, Dufournel D, Stodulka P, Romano F, Bernard A. Comparison of ultrasound phacoemulsification and FemtoMatrix® PhotoEmulsification® cataract surgery. Front Med. 2023;10(April):1–7.

Tati V, Mitra S, Basu S, Shukla S. Bone marrow mesenchymal stem cell-derived extracellular vesicles promote corneal epithelial repair and suppress apoptosis via modulation of Caspase-3 in vitro. FEBS Open Bio. 2024;14(6):968–82.

Staehlke S, Mahajan S, Thieme D, Trosan P, Fuchsluger TA. Suppressing Pro-Apoptotic Proteins by siRNA in Corneal Endothelial Cells Protects against Cell Death. Biomedicines. 2024;12(7).

Fidianto A, Komaratih E, Sasono W, Sandhika W, Notobroto HB. Intracameral injection of limbal mesenchymal stem cells secretome alleviate inflammation with delayed structural recovery on corneal endothelial cells in phacoemulsified rabbit eyes. Biochem Cell Arch. 2019;19:4729–36.

Yang C, An Q, Zhou H, Ge H. Research progress on the impact of cataract surgery on corneal endothelial cells. Adv Ophthalmol Pract Res. 2024;4(4):194–201.

Mitchell R, Mellows B, Sheard J, Antonioli M, Kretz O, Chambers D, et al. Secretome of adipose-derived mesenchymal stem cells promotes skeletal muscle regeneration through synergistic action of extracellular vesicle cargo and soluble proteins. Stem Cell Res Ther. 2019;10(1):1–19.

Nadesh R, Menon KN, Biswas L, Mony U, Subramania Iyer K, Vijayaraghavan S, et al. Adipose derived mesenchymal stem cell secretome formulation as a biotherapeutic to inhibit growth of drug resistant triple negative breast cancer. Sci Rep [Internet]. 2021;11(1):1–13. Available from: https://doi.org/10.1038/s41598-021-01878-z

Hoang DM, Pham PT, Bach TQ, Ngo ATL, Nguyen QT, Phan TTK, et al. Stem cell-based therapy for human diseases. Signal Transduct Target Ther. 2022;7(1).

Hermawan D, Sudiana IK, Komaratih E, Ihsan IS. Comparison of IL-10 , TGF- β1 , and VEGF Levels in The Secretome of Limbus, Adipose, and Bone Marrow Mesenchymal Stem Cells. Nanotechnol Perceptions. 2024;20(13).

Trzyna A, Banaś-Ząbczyk A. Adipose-derived stem cells secretome and its potential application in “stem cell-free therapy.” Biomolecules. 2021;11(6).

Yamashita K, Hatou S, Inagaki E, Higa K, Tsubota K, Shimmura S. A Rabbit Corneal Endothelial Dysfunction Model Using Endothelial-Mesenchymal Transformed Cells. Sci Rep [Internet]. 2018;8(1):1–11. Available from: http://dx.doi.org/10.1038/s41598-018-35110-2

Yao X, Devarajan K, Werkmeister RM, dos Santos VA, Ang M, Kuo A, et al. In vivo corneal endothelium imaging using ultrahigh resolution OCT. Biomed Opt Express. 2019;10(11):5675.

Calasans-Maia MD, Monteiro ML, Áscoli FO, Granjeiro JM. The rabbit as an animal model for experimental surgery. Acta Cir Bras. 2009;24(4):325–8.

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Published

2025-04-18

How to Cite

1.
Perwitasari BH, Komaratih E, Hermawan D. Literature Review: The Role of Adipose Stem Cell Secretome In Caspase-3 Regulation and Endothelial Cell Density Preservation in Corneal Regeneration Post-Phacoemulsification. J Neonatal Surg [Internet]. 2025Apr.18 [cited 2025Sep.22];14(14S):728-32. Available from: https://www.jneonatalsurg.com/index.php/jns/article/view/4037