Lens regeneration

Last updated
Examination of a child with cataracts Doctor and technician team revive Afghan youth's vision 130707-F-IW762-952.jpg
Examination of a child with cataracts

The regeneration of the lens of the eye has been studied, mostly in amphibians and rabbits, from the 18th century. In the 21st century, an experimental medical trial has been performed in humans as this is a promising technique for treating cataracts, especially in children.

Contents

History

In 1781, Charles Bonnet found that a salamander had regenerated an eye one year after most of it, including the lens, had been removed. [1] Vincenzo Colucci made a histological study of the phenomenon in newts, publishing his finding that it regenerated from the iris in 1891. [1] Gustav Wolff then published several papers on the topic, starting in 1895, and this form of regeneration is now called Wolffian regeneration. [1] The priority issue between Colucci and Wolff is examined in more detail by Holland (2021). [2]

Regeneration of the lens in rabbits was first studied by French surgeons Cocteau and Leroy-D'Étiolle, starting in 1824. [3] The crystallin contents of the lens capsule were removed but this was found to regenerate within a month. [4] cThe rabbit is suitable for development of surgical techniques on the eye because it is easy to handle and its eye is comparatively large. [5] Research in rabbits showed that their lens would start to regenerate within two weeks after a capsulotomy – a surgical technique in which the crystalline lens material is removed but the surrounding capsule which contained it is left mostly intact. [6] The new lens was similar in structure to the structure but its shape might be irregular. [6] Filling the capsule during regeneration seemed to encourage development of a more normal shape. [6] The technique was also found to work in primates and so has been studied as a possible technique for treating cataracts in humans. [6] Other animals in which lens regeneration has been observed include cats, chickens, dogs, fish, mice, rats and Xenopus frogs. [7]

Experimental trials

A lens regeneration technique was trialled in a collaboration between Sun Yat-sen University and University of California, San Diego which was published in 2016. [8] The capsule of the lens was pierced with a smaller cut than in conventional cataract surgery – just 1–1.5 mm – and drained of its contents clouding the vision causing cataracts. The capsule was otherwise left intact as this is lined with lens epithelial stem cells, which then reproduced to regenerate the lens. The technique was performed successfully in experiments in rabbits and macaques, and subsequently in a trial of twelve children under two years in China who had been born with cataracts. Working lenses regenerated within six to eight months. [9] [10]

The children treated with the experimental technique experienced fewer complications than twenty-five children treated by conventional surgery. [10] Children are the most promising subjects because their stem cells are more vigorous than in adults. Also, conventional treatment of childhood cataracts using an artificial lens can cause complications in children because they are still growing. [9] The technique has yet to be tried with older patients with age-related cataracts, but is expected to be less successful. Adult cataracts are more difficult to remove and adult lens stem cells regenerate more slowly. [10]

In vitro techniques

Another regenerative technique is to grow eye tissues, such as the lens, outside the body and then to implant it. This has been tried in a collaboration between Osaka University and Cardiff University. [9]

Mechanisms

The regeneration of the lens has been studied in several vertebrate species, especially the newt, which is able to repeatedly regenerate a perfect lens. [11] One study found that the lens of a newt that had been extracted and regenerated 18 times was indistinguishable from the lens of a control newt in terms of appearance and gene expression. [12] In such cases, the lens has been found to regenerate completely from epithelial cells in the cornea or iris. [13] The signalling mechanisms which control this process include fibroblast growth factor, hedgehog, retinoic acid, transforming growth factor beta and wnt. [13] The Haotian, Hong, Jie, Shan trial conducted experiments on mice, rabbits and cultured human cells and reported that the proteins produced by the PAX6 and BMI1 genes were essential for regeneration of existing lens epithelial cells (LECs) lining the lens capsule. [8]

Related Research Articles

Cataract Clouding of the lens inside the eye, which leads to low vision

A cataract is a cloudy area in the lens of the eye that leads to a decrease in vision. Cataracts often develop slowly and can affect one or both eyes. Symptoms may include faded colors, blurry or double vision, halos around light, trouble with bright lights, and trouble seeing at night. This may result in trouble driving, reading, or recognizing faces. Poor vision caused by cataracts may also result in an increased risk of falling and depression. Cataracts cause half of all cases of blindness and 33% of visual impairment worldwide.

Lens (anatomy) Eye structure

The lens, or crystalline lens is a transparent biconvex structure in the eye that, along with the cornea, helps to refract light to be focused on the retina. By changing shape, it functions to change the focal length of the eye so that it can focus on objects at various distances, thus allowing a sharp real image of the object of interest to be formed on the retina. This adjustment of the lens is known as accommodation. Accommodation is similar to the focusing of a photographic camera via movement of its lenses. The lens is flatter on its anterior side than on its posterior side.

Cornea Transparent front layer of the eye

The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Along with the anterior chamber and lens, the cornea refracts light, accounting for approximately two-thirds of the eye's total optical power. In humans, the refractive power of the cornea is approximately 43 dioptres. The cornea can be reshaped by surgical procedures such as LASIK.

LASIK Corrective ophthalmological surgery

LASIK or Lasik, commonly referred to as laser eye surgery or laser vision correction, is a type of refractive surgery for the correction of myopia, hyperopia, and an actual cure for astigmatism, since it is in the cornea. LASIK surgery is performed by an ophthalmologist who uses a laser or microkeratome to reshape the eye's cornea in order to improve visual acuity. For most people, LASIK provides a long-lasting alternative to eyeglasses or contact lenses.

Photorefractive keratectomy Eye surgery

Photorefractive keratectomy (PRK) and laser-assisted sub-epithelial keratectomy (LASEK) are laser eye surgery procedures intended to correct a person's vision, reducing dependency on glasses or contact lenses. LASEK and PRK permanently change the shape of the anterior central cornea using an excimer laser to ablate a small amount of tissue from the corneal stroma at the front of the eye, just under the corneal epithelium. The outer layer of the cornea is removed prior to the ablation.

Radial keratotomy Refractive surgical procedure to correct myopia (nearsightedness

Radial keratotomy (RK) is a refractive surgical procedure to correct myopia (nearsightedness). It was developed in 1974 by Svyatoslav Fyodorov, a Russian ophthalmologist. It has been largely supplanted by newer operations, such as photorefractive keratectomy, LASIK, Epi-LASIK and the phakic intraocular lens. Approximately 10% of all practicing ophthalmologists in the United States have performed several hundred thousand RK procedures.

Refractive surgery Medical specialty

Refractive eye surgery is optional eye surgery used to improve the refractive state of the eye and decrease or eliminate dependency on glasses or contact lenses. This can include various methods of surgical remodeling of the cornea (keratomileusis), lens implantation or lens replacement. The most common methods today use excimer lasers to reshape the curvature of the cornea. Refractive eye surgeries are used to treat common vision disorders such as myopia, hyperopia, presbyopia and astigmatism.

Phacoemulsification Type of cataract surgery

Phacoemulsification is a modern cataract surgery method in which the eye's internal lens is emulsified with an ultrasonic handpiece and aspirated from the eye. Aspirated fluids are replaced with irrigation of balanced salt solution to maintain the anterior chamber.

Intraocular lens Lens implanted in the eye to treat cataracts or myopia

Intraocular lens (IOL) is a lens implanted in the eye as part of a treatment for cataracts or myopia. If the natural lens is left in the eye, the IOL is known as phakic, otherwise it is a pseudophakic, or false lens. Such a lens is typically implanted during cataract surgery, after the eye's cloudy natural lens (cataract) has been removed. The pseudophakic IOL provides the same light-focusing function as the natural crystalline lens. The phakic type of IOL is placed over the existing natural lens and is used in refractive surgery to change the eye's optical power as a treatment for myopia (nearsightedness). This is an alternative to LASIK.

Regeneration (biology) Biological process of renewal, restoration, and tissue growth

In biology, regeneration is the process of renewal, restoration, and tissue growth that makes genomes, cells, organisms, and ecosystems resilient to natural fluctuations or events that cause disturbance or damage. Every species is capable of regeneration, from bacteria to humans. Regeneration can either be complete where the new tissue is the same as the lost tissue, or incomplete where after the necrotic tissue comes fibrosis.

Cataract surgery Surgery for the eye

Cataract surgery, also called lens replacement surgery, is the removal of the natural lens of the eye that has developed an opacification, which is referred to as a cataract, and its replacement with an intraocular lens. Metabolic changes of the crystalline lens fibers over time lead to the development of the cataract, causing impairment or loss of vision. Some infants are born with congenital cataracts, and certain environmental factors may also lead to cataract formation. Early symptoms may include strong glare from lights and small light sources at night, and reduced acuity at low light levels.

Corneal cross-linking Surgical procedure

Corneal cross-linking with riboflavin (vitamin B2) and UV-A light is a surgical treatment for corneal ectasia such as keratoconus, PMD, and post-LASIK ectasia.

Sankara Nethralaya Hospital in Chennai, Kolkata

Sankara Nethralaya is a not-for-profit missionary institution for ophthalmic care headquartered in Chennai, India. In the name "Sankara Nethralaya", "Sankara" is a reference to Adi Shankaracharya and "Nethralaya" means "The Temple of the Eye". Sankara Nethralaya receives patients from India and abroad. Sankara Nethralaya has over 1000 employees and serves around 1500 patients per day, performing over 100 surgeries per day. The annual revenue as per the taxes is close to US$100 million.

Capsulorhexis or capsulorrhexis, also known as continuous curvilinear capsulorhexis (CCC), is a technique pioneered by Howard Gimbel used to remove the capsule of the lens from the eye during cataract surgery by shear and stretch forces. It generally refers to removal of a part of the anterior lens capsule, but in situations like a developmental cataract a part of the posterior capsule is also removed by a similar technique.

Capsulotomy

Capsulotomy is a type of eye surgery in which an incision is made into the capsule of the crystalline lens of the eye. In modern cataract operations, the lens capsule is usually not removed. The most common forms of cataract surgery remove nearly all of the crystalline lens but do not remove the crystalline lens capsule. The crystalline lens capsule is retained and used to contain and position the intraocular lens implant (IOL).

Regeneration in humans is the regrowth of lost tissues or organs in response to injury. This is in contrast to wound healing, or partial regeneration, which involves closing up the injury site with some gradation of scar tissue. Some tissues such as skin, the vas deferens, and large organs including the liver can regrow quite readily, while others have been thought to have little or no capacity for regeneration following an injury.

Limbal stem cell

Limbal stem cells, also known as corneal epithelial stem cells, are stem cells located in the basal epithelial layer of the corneal limbus. They form the border between the cornea and the sclera. Characteristics of limbal stem cells include a slow turnover rate, high proliferative potential, clonogenicity, expression of stem cell markers, as well as the ability to regenerate the entire corneal epithelium. Limbal stem cell proliferation has the role of maintaining the cornea; for example, by replacing cells that are lost via tears. Additionally, these cells also prevent the conjunctival epithelial cells from migrating onto the surface of the cornea.

Hox genes in amphibians and reptiles

Hox genes play a massive role in some amphibians and reptiles in their ability to regenerate lost limbs, especially HoxA and HoxD genes.

IOL Scaffold or Intraocular lens Scaffold technique is a surgical procedure in Ophthalmology. In cases where the lens bag is ruptured and the cataract of the eye is not yet removed one can inject an artificial lens or Intraocular lens (IOL) inside the eye under the cataract. This way the IOL acts as a scaffold and prevents the cataract pieces from falling inside the eye. One can then remove the cataract pieces safely by emulsifying it with ultrasound. This technique is called IOL Scaffold and was started by Dr. Amar Agarwal from Chennai, India at Dr. Agarwal's Eye Hospital.

Dedifferentiation is a transient process by which cells become less specialized and return to an earlier cell state within the same lineage. This suggests an increase in a cell potency, meaning that after dedifferentiation, cells may possess an ability to redifferentiate into more cell types than it did before. This is in contrast to differentiation, where differences in gene expression, morphology, or physiology arise in a cell, making its function increasingly specialized.

References

  1. 1 2 3 R. W. Reyer (2013), "The Amphibian Eye: Development and Regeneration", in Crescitelli (ed.), The Visual System in Vertebrates, Springer Science & Business, pp. 310–311, 338–362, ISBN   9783642664687
  2. Holland, Nicholas (2021), "Vicenzo Colucci's 1886 memoir, Intorno alla rigenerazione degli arti e della coda nei tritoni, annotated and translated into English as: Concerning regeneration of the limbs and tail in salamanders", The European Zoological Journal, 88: 837–890, doi:10.1080/24750263.2021.1943549, S2CID   238904520
  3. Cocteau; Leroy-D'Étiolle (1827), François Magendie (ed.), "Expériences Relatives a la Reproduction du Cristallin", Journal de Physiologie Expérimentale et Pathologique, 7 (1): 30–44
  4. Nathan Ryno Smith, ed. (July 1827), "Regeneration of the Chrystaline Humour", The Philadelphia Monthly Journal of Medicine and Surgery, 1 (2): 99
  5. Gwon, Arlene (2011), "The Rabbit in Cataract/IOL Surgery", Animal Models in Eye Research, Academic Press, pp. 184, 187, ISBN   9780080921037
  6. 1 2 3 4 Gwon, Arlene (2006), "Lens Regeneration in Mammals: A Review", Survey of Ophthalmology, 51 (1): 51–62, doi:10.1016/j.survophthal.2005.11.005, PMID   16414361
  7. Barbosa-Sabanero; Hoffmann; Judge; Lightcap; Tsonis; Del Rio-Tsonis (2012), "Lens and retina regeneration: new perspectives from model organisms", Biochemical Journal, 447 (3): 321–334, doi:10.1042/BJ20120813, PMID   23035979
  8. 1 2 Haotian Lin; Hong Ouyang; Jie Zhu; et al. (2016), "Lens regeneration using endogenous stem cells with gain of visual function", Nature , 531 (7594): 323–8, Bibcode:2016Natur.531..323L, doi:10.1038/nature17181, PMC   6061995 , PMID   26958831
  9. 1 2 3 Gallagher, James (9 March 2016), 'Stunning' operation regenerates eye's lens, BBC News
  10. 1 2 3 Bazian (10 March 2016), Stem cells used to repair children's eyes after cataracts, National Health Service , retrieved 10 March 2016
  11. Brown, Mark (13 July 2011), "Biologists pull out a newt's eye lens 18 times to test regeneration", Wired
  12. Eguchi G, Eguchi Y, Nakamura K, Yadav MC, Millán JL, Tsonis PA (2011), "Regenerative capacity in newts is not altered by repeated regeneration and ageing", Nature Communications , 2: 384, Bibcode:2011NatCo...2..384E, doi:10.1038/ncomms1389, PMC   3144589 , PMID   21750538
  13. 1 2 Henry, Jonathan; Thomas, Alvin; Hamilton, Paul; Moore, Lisa; Perry, Kimberly (8 December 2012), Cell Signaling Pathways in Vertebrate Lens Regeneration, Current Topics in Microbiology and Immunology, vol. 367, Springer, pp. 75–98, doi:10.1007/82_2012_289, ISBN   978-3-642-35809-8, ISSN   0070-217X, PMC   4304700 , PMID   23224710

Further reading