Crystalline Conundrum: Understanding the Absence of Tumorigenesis in the Human Lens
DOI:
https://doi.org/10.65539/jrq4yp41Keywords:
primary lens tumor, tumorigenesis, cancer preventionAbstract
Despite the mitotically active nature of the ocular lens and near-constant exposure to ultraviolet radiation, there have been no reported cases of primary tumors in the human lens. In contrast, such tumors have been induced and reported in the lens of non-human vertebrates, particularly in cats. This report discusses various theories, including the avascular nature of the lens, the presence of barrier properties within the ocular environment, and the lens capsule composition as a potential chemo-mechanical barrier against tumorigenesis. Identifying protective mechanisms could contribute to a better understanding of human cancer genetics and potentially lead to preventative treatments.
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1. Sachs E, Larsen RL. Cancer and the Lens. Am J Ophthalmol. 1948;31(5):561-564. doi:10.1016/0002-9394(48)90558-3 DOI: https://doi.org/10.1016/0002-9394(48)90558-3
2. Ullrich K, Casson RJ. Does anybody care that the crystalline lens never gets cancer? Clin Experiment Ophthalmol. 2013;41(8):812-812. doi:10.1111/ceo.12114 DOI: https://doi.org/10.1111/ceo.12114
3. Mann I. Induction of an Experimental Tumour of the Lens. Br J Ophthalmol. 1947;31(11):676-685. doi:10.1136/bjo.31.11.676 DOI: https://doi.org/10.1136/bjo.31.11.676
4. M. Seigel G. The enigma of lenticular oncology. Digit J Ophthalmol. 2001;7(4). Accessed December 13, 2023. https://legacy.djo.harvard.edu/site.php%3Furl=%252Fphysicians%252Foa%252F360.html
5. Domazet-Lošo T, Klimovich A, Anokhin B, et al. Naturally occurring tumours in the basal metazoan Hydra. Nat Commun. 2014;5(1):4222. doi:10.1038/ncomms5222 DOI: https://doi.org/10.1038/ncomms5222
6. Lens and Cataract, Chapter 2: Anatomy. In: 2020–2021 BCSC Basic and Clinical Science Course. American Academy of Ophthalmology. Accessed December 13, 2023. https://www.aao.org/education/bcscsnippetdetail.aspx?id=298pd36-d41e-4714-80d9-f55e41ec4624
7. Von Sallmann L, E. Halver J, Collins E, Grimes P. Thioacetamide-induced Cataract with Invasive Proliferation of the Lens Epithelium in Rainbow Trout. Cancer Res. 1966;26:1819-1825.
8. Albert DM, Rabson AS, Grimes PA, Von Sallmann L. Neoplastic Transformation in vitro of Hamster Lens Epithelium by Simian Virus 40. Science. 1969;164(3883):1077-1078. doi:10.1126/science.164.3883.1077 DOI: https://doi.org/10.1126/science.164.3883.1077
9. Chen Q, Hung FC, Fromm L, Overbeek PA. Induction of cell cycle entry and cell death in postmitotic lens fiber cells by overexpression of E2F1 or E2F2. Invest Ophthalmol Vis Sci. 2000;41(13):4223-4231.
10. Zheng H chuan, Nakamura T, Zheng Y, et al. SV40 T antigen disrupted the cell metabolism and the balance between proliferation and apoptosis in lens tumors of transgenic mice. J Cancer Res Clin Oncol. 2009;135(11):1521-1532. doi:10.1007/s00432-009-0599-z DOI: https://doi.org/10.1007/s00432-009-0599-z
11. Mahon KA, Chepelinsky AB, Khillan JS, Overbeek PA, Piatigorsky J, Westphal H. Oncogenesis of the Lens in Transgenic Mice. Science. 1987;235(4796):1622-1628. doi:10.1126/science.3029873 DOI: https://doi.org/10.1126/science.3029873
12. Woog J, Albert DM, Gonder JR, Carpenter JJ. Osteosarcoma in a Phthisical Feline Eye. Vet Pathol. 1983;20(2):209-214. doi:10.1177/030098588302000208 DOI: https://doi.org/10.1177/030098588302000208
13. Dubielzig RR. Ocular sarcoma following trauma in three cats. J Am Vet Med Assoc. 1984;184(5):578-581. DOI: https://doi.org/10.2460/javma.1984.184.05.578
14. Dubielzig RR, Everitt J, Shadduck JA, Albert DM. Clinical and Morphologic Features of Post-traumatic Ocular Sarcomas in Cats. Vet Pathol. 1990;27(1):62-65. doi:10.1177/030098589002700111 DOI: https://doi.org/10.1177/030098589002700111
15. Wong CJ, Peiffer RL, Oglesbee S, Osborne C. Feline ocular epithelial response to growth factors in vitro. Am J Vet Res. 1996;57(12):1748-1752. DOI: https://doi.org/10.2460/ajvr.1996.57.12.1748
16. Zeiss CJ, Johnson EM, Dubielzig RR. Feline intraocular tumors may arise from transformation of lens epithelium. Vet Pathol. 2003;40(4):355-362. doi:10.1354/vp.40-4-355 DOI: https://doi.org/10.1354/vp.40-4-355
17. Carter RT, Giudice C, Dubielzig RR, Colitz CMH. Telomerase Activity with Concurrent Loss of Cell Cycle Regulation in Feline Post-traumatic Ocular Sarcomas. J Comp Pathol. 2005;133(4):235-245. doi:10.1016/j.jcpa.2005.04.009 DOI: https://doi.org/10.1016/j.jcpa.2005.04.009
18. McPherson L, Newman SJ, McLean N, et al. Intraocular Sarcomas in Two Rabbits. J Vet Diagn Invest. 2009;21(4):547-551. doi:10.1177/104063870902100422 DOI: https://doi.org/10.1177/104063870902100422
19. Dickinson R, Bauer B, Gardhouse S, Grahn B. Intraocular sarcoma associated with a rupture lens in a rabbit ( Oryctolagus cuniculus ). Vet Ophthalmol. 2013;16(s1):168-172. doi:10.1111/vop.12049 DOI: https://doi.org/10.1111/vop.12049
20. M. Albert D, O. Phelps P, R. Surapaneni K, et al. The Significance of the Discordant Occurrence of Lens Tumors in Humans versus Other Species. Ophthalmology. 2015;122(9). DOI: https://doi.org/10.1016/j.ophtha.2015.05.028
21. March 2015 Report to the Congress: Medicare Payment Policy – MedPAC. Accessed December 13, 2023. https://www.medpac.gov/document/http-www-medpac-gov-docs-default-source-reports-mar2015_entirereport_revised-pdf/
22. H. D. The Lens. In: Physiology of the Eye. 5th ed. New York Pergamon Press; :145-149.
23. Folkman J, Merler E, Abernathy C, Williams G. Isolation of a tumor factor responsible for angiogenesis. J Exp Med. 1971;133(2):275-288. DOI: https://doi.org/10.1084/jem.133.2.275
24. Chaturvedi S, Mehrotra AN, Mittal S, Bahadur H. The Conundrum of Lenticular Oncology. A Review. Indian J Ophthalmol. 2003;51(4):297.
25. Langer R, Brem H, Falterman K, Klein M, Folkman J. Isolations of a Cartilage Factor That Inhibits Tumor Neovascularization. Science. 1976;193(4247):70-72. doi:10.1126/science.935859 DOI: https://doi.org/10.1126/science.935859
26. Pettenati MJ, Sweatt AJ, Lantz P, et al. The human cornea has a high incidence of acquired chromosome abnormalities. Hum Genet. 1997;101(1):26-29. doi:10.1007/s004390050580 DOI: https://doi.org/10.1007/s004390050580
27. Marshall GE, Konstas AGP, Bechrakis NE, Lee WR. An immunoelectron microscope study of the aged human lens capsule. Exp Eye Res. 1992;54(3):393-401. doi:10.1016/0014-4835(92)90051-S DOI: https://doi.org/10.1016/0014-4835(92)90051-S
28. Schmut O. The organization of tissues of the eye by different collagen types. Albrecht Von Graefes Arch Für Klin Exp Ophthalmol. 1978;207(3):189-199. doi:10.1007/BF00411053 DOI: https://doi.org/10.1007/BF00411053
29. Sasaki T, Larsson H, Tisi D, Claesson-Welsh L, Hohenester E, Timpl R. Endostatins derived from collagens XV and XVIII differ in structural and binding properties, tissue distribution and anti-angiogenic activity11Edited by A. Fersht. J Mol Biol. 2000;301(5):1179-1190. doi:10.1006/jmbi.2000.3996 DOI: https://doi.org/10.1006/jmbi.2000.3996
30. Kefalides NA, Monboisse JC, Bellon G, Ohno N, Ziaie Z, Shahan TA. Suppression of tumor cell growth by type IV collagen and a peptide from the NC1 domain of the alpha 3(IV) chain. Medicina (Mex). 1999;59(5 Pt 2):553.
31. Pasco S, Han J, Gillery P, et al. A specific sequence of the noncollagenous domain of the alpha3(IV) chain of type IV collagen inhibits expression and activation of matrix metalloproteinases by tumor cells. Cancer Res. 2000;60(2):467-473.
32. Webber P, Landis B, Loveless B, C Pappas A. Paradoxical lack of investigation into the natural tumor-resistant properties of the human lens capsular epithelium. Invest Ophthalmol Vis Sci. 2023;64(8):4140.
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