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Year : 2020  |  Volume : 10  |  Issue : 1  |  Page : 1-2

New strategy to restore ocular surface health

Ocular Surface Center, Ocular Surface Research Education Foundation, and R&D Department of TissueTech Inc., Miami, FL, USA

Date of Web Publication04-Mar-2020

Correspondence Address:
Dr., MD, PhD Scheffer C. G. Tseng
Ocular Surface Center, Ocular Surface Research Education Foundation, and R&D Department of TissueTech Inc., Miami, FL
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/tjo.tjo_78_19

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How to cite this article:
Tseng SC. New strategy to restore ocular surface health. Taiwan J Ophthalmol 2020;10:1-2

How to cite this URL:
Tseng SC. New strategy to restore ocular surface health. Taiwan J Ophthalmol [serial online] 2020 [cited 2021 Sep 20];10:1-2. Available from: https://www.e-tjo.org/text.asp?2020/10/1/1/279987

The ocular surface, consisting of both the cornea and conjunctiva, is the only wetted body surface that is directly exposed to the outside environment. This mother-nature design was developed through evolution and is essential to maintain ocular surface health so that one may enjoy clear vision without suffering from discomfort due to dryness in the open-eye state. In this Issue, Mead et al.,[1] points out that the neuroanatomic integration of the ocular surface epithelia with the external adnexae, i.e., eyelids, lacrimal glands, and  Meibomian gland More Detailss, is the operating mechanism to ensure ocular surface health. These diverse components are integrated into one unit by the first branch of the trigeminal nerve, which triggers tearing (compositional) and blinking (hydrodynamic) reflexes to maintain a stable preocular tear film. The concept of neuroanatomic integration explains why corneal pathologies are overlapped in two seemingly different diseases, i.e., neurotrophic keratitis and dry eye disease, once we realize that there is a progressive loss of subbasal corneal nerve density with increasing severity of the latter. For the rest of the body, taking diabetic foot ulcers as an example,[2] ischemia is the primary cause of nonhealing ulcers. As the cornea is avascular and already setup for ischemia, its source of oxygen depends on a stable precorneal tear film when the eye is open. To further compensate for this avascular “ischemic” state, the cornea is endowed with the most highly innervated tissue in the body to drive the aforementioned neuroanatomic integration. Therefore, the neuroanatomic integration also explains why neurotrophic keratitis causes the worst form of dry eye and is the prime cause of persistent epithelial defect and nonhealing ulcers for the cornea.

Also summarized by Mead et al.,[1] transplantation of cryopreserved human amniotic membrane has become one novel strategy to promote wound healing for patients suffering from neurotrophic keratitis. Insertion of PROKERA® is now a convenient way of performing amniotic membrane transplantation in the clinic not only to promote healing in patients with neurotrophic keratitis and ulcers but also to restore corneal surface integrity in patients with moderate to severe dry eye disease. Chronic inflammation is a well-known, common pathological denominator for both neurotrophic keratitis and dry eye diseases; not only has cryopreserved amniotic membrane been shown to reduce inflammation, but it most excitingly has been shown to promote corneal nerve regeneration.[3]

Since our first reintroduction of amniotic membrane transplantation in ophthalmology in 1995,[4] a myriad of plausible mechanisms had been proposed to explain how amniotic membrane transplantation works by 2004.[5] Nearly one decade from that time, our laboratory has been devoted to searching for the molecular candidate responsible for the amniotic membrane's therapeutic actions. From water-soluble amniotic membrane extract, we have purified heavy chain (HC)-hyaluronic acid (HA)/pentraxin 3 (PTX3) consisting of high molecular weight HA covalently linked with HC1 from inter-α-trypsin inhibitor (“-” denotes covalent linkage) and further complexed with PTX3 (”/” denotes noncovalent linkage).[6],[7] As summarized by Tighe et al.,[8] HC-HA/PTX3 is a unique matrix abundantly present in the birth tissue, i.e., amniotic membrane and umbilical cord. As a single agent, HC-HA/PTX3 orchestrates a number of biological actions in several cell types. Its actions toward neutrophils, macrophages, and lymphocytes translate into a broad-spectrum anti-inflammatory action that extends from innate to adaptive immune responses. HC-HA/PTX3 also exerts anti-scarring action to prevent myofibroblast differentiation. Furthermore, HC-HA/PTX3 supports limbal niche cells to maintain quiescence of limbal epithelial stem cells. These actions collectively support why transplantation of amniotic membrane augments the success of in vivo[9],[10],[11] and ex vivo[12],[13],[14] expansion of limbal epithelial stem cells to treat corneal blindness caused by limbal stem cell deficiency. Further research is underway to explore how HC-HA/PTX3 might aid in nerve regeneration. Collectively, these actions render HC-HA/PTX3 as the prime candidate in the birth tissue to deliver regenerative healing.[15] These regenerative properties of HC-HA/PTX3 in the birth tissue have been demonstrated not only in ophthalmology as summarized by Mead et al.,[1] but also beyond ophthalmology in diabetic foot ulcers,[16] spina bifida,[17] surgical reconstruction of extremities,[18] and radical prostatectomy.[19] Thus, one may imagine that regenerative treatment through the use of the birth tissue may one day become a new biologic strategy not only to restore ocular surface health but also to fulfill unmet clinical needs in many degenerative diseases that prevail beyond the ocular surface.

  References Top

Mead OG, Tighe S, Tseng SC. Amniotic membrane transplantation for managing dry eye and neurotrophic keratitis. Taiwan J Ophthalmol 2020;10:13-21.  Back to cited text no. 1
  [Full text]  
Meloni M, Izzo V, Giurato L, Gandini R, Uccioli L. Below-the-ankle arterial disease severely impairs the outcomes of diabetic patients with ischemic foot ulcers. Diabetes Res Clin Pract 2019;152:9-15.  Back to cited text no. 2
John T, Tighe S, Sheha H, Hamrah P, Salem ZM, Cheng AMS, et al. Corneal nerve regeneration after self-retained cryopreserved amniotic membrane in dry eye disease. J Ophthalmol 2017;2017:6404918.  Back to cited text no. 3
Kim JC, Tseng SC. Transplantation of preserved human amniotic membrane for surface reconstruction in severely damaged rabbit corneas. Cornea 1995;14:473-84.  Back to cited text no. 4
Tseng SC, Espana EM, Kawakita T, Di Pascuale MA, Li W, He H, et al. How does amniotic membrane work? Ocul Surf 2004;2:177-87.  Back to cited text no. 5
He H, Li W, Tseng DY, Zhang S, Chen SY, Day AJ, et al. Biochemical characterization and function of complexes formed by hyaluronan and the heavy chains of inter-alpha-inhibitor (HC*HA) purified from extracts of human amniotic membrane. J Biol Chem 2009;284:20136-46.  Back to cited text no. 6
Zhang S, Zhu YT, Chen SY, He H, Tseng SC. Constitutive expression of pentraxin 3 (PTX3) protein by human amniotic membrane cells leads to formation of the heavy chain (HC)-hyaluronan (HA)-PTX3 complex. J Biol Chem 2014;289:13531-42.  Back to cited text no. 7
Tighe S, Mead OG, Lee A, Tseng SC. Basic science review of birth tissue uses in ophthalmology. Taiwan J Ophthalmol 2020;10:3-12.  Back to cited text no. 8
  [Full text]  
Anderson DF, Ellies P, Pires RT, Tseng SC. Amniotic membrane transplantation for partial limbal stem cell deficiency. Br J Ophthalmol 2001;85:567-75.  Back to cited text no. 9
Gomes JA, dos Santos MS, Cunha MC, Mascaro VL, Barros Jde N, de Sousa LB. Amniotic membrane transplantation for partial and total limbal stem cell deficiency secondary to chemical burn. Ophthalmology 2003;110:466-73.  Back to cited text no. 10
Meallet MA, Espana EM, Grueterich M, Ti SE, Goto E, Tseng SC. Amniotic membrane transplantation with conjunctival limbal autograft for total limbal stem cell deficiency. Ophthalmology 2003;110:1585-92.  Back to cited text no. 11
Tsai RJ, Li LM, Chen JK. Reconstruction of damaged corneas by transplantation of autologous limbal epithelial cells. N Engl J Med 2000;343:86-93.  Back to cited text no. 12
Sangwan VS, Vemuganti GK, Singh S, Balasubramanian D. Successful reconstruction of damaged ocular outer surface in humans using limbal and conjuctival stem cell culture methods. Biosci Rep 2003;23:169-74.  Back to cited text no. 13
Kawashima M, Kawakita T, Satake Y, Higa K, Shimazaki J. Phenotypic study after cultivated limbal epithelial transplantation for limbal stem cell deficiency. Arch Ophthalmol 2007;125:1337-44.  Back to cited text no. 14
Tseng SC. HC-HA/PTX3 purified from amniotic membrane as novel regenerative matrix: Insight Into relationship between inflammation and regeneration. Invest Ophthalmol Vis Sci 2016;57:ORSFh1-8.  Back to cited text no. 15
Marston WA, Lantis JC 2nd, Wu SC, Nouvong A, Lee TD, McCoy ND, et al. An open-label trial of cryopreserved human umbilical cord in the treatment of complex diabetic foot ulcers complicated by osteomyelitis. Wound Repair Regen 2019;27:680-6.  Back to cited text no. 16
Papanna R, Moise KJ Jr., Mann LK, Fletcher S, Schniederjan R, Bhattacharjee MB, et al. Cryopreserved human umbilical cord patch for in-utero spina bifida repair. Ultrasound Obstet Gynecol 2016;47:168-76.  Back to cited text no. 17
Bemenderfer TB, Anderson RB, Odum SM, Davis WH. Effects of cryopreserved amniotic membrane-umbilical cord allograft on total ankle arthroplasty wound healing. J Foot Ankle Surg 2019;58:97-102.  Back to cited text no. 18
Ahmed M, Esposito M, Lovallo G. A single-center, retrospective review of robot-assisted laparoscopic prostatectomy with and without cryopreserved umbilical cord allograft in improving continence recovery. J Robot Surg 2019. doi:10.1007/s11701-019-00972-9.  Back to cited text no. 19

This article has been cited by
1 Letter to the editor: PROKERAź slim corneal bandage now approved in Taiwan for treatment of corneal diseases
SchefferC. G. Tseng
Taiwan Journal of Ophthalmology. 2020; 0(0): 0
[Pubmed] | [DOI]


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