Tissue aids glaucoma surgery

Orlando, FL-The use of cryopreserved amniotic membrane tissue on the ocular surface can modulate inflammation and promote healing without scarring in adults.

Scheffer C.G. Tseng, MD, PhD, discussed the role of cryopreserved amniotic membrane in glaucoma surgery and described his research into how cryopreserved amniotic membrane works during Glaucoma Subspecialty Day at the annual meeting of the American Academy of Ophthalmology.

"The use of cryopreserved amniotic membrane is based on a totally different approach to adult wound healing," said Dr. Tseng, medical director of the Ocular Surface Center, and chief scientific officer for TissueTech Inc.

Amniotic membrane technology is currently subdivided into three areas: use as a biologic bandage, permanent grafts, and tectonic support. For grafting, different thickness of grafts are available (AmnioGraft and AmnioGraft-G, 100 and 300 µm thick, respectively). These tissues can be substitutes for epithelial tissue and act as a barrier to prevent adhesion. The membranes can be delivered without the need for sutures through the use of ProKera, a type II medical device that modulates ocular surface wound healing. AmnioGuard is a 400-µm thick tissue with higher tensile strength that can be used as scleral reinforcement and to cover glaucoma tubes, he explained.

All of these products are manufactured by Bio-Tissue Inc., which licensed the technology from TissueTech Inc.

Adult wound healing

This is a complex process that starts with coagulation and progresses through inflammation, formation of granulation tissue, re-epithelialization, angiogenesis, and ultimately reaches remodeling.

"In this pathway, there are three critical cellular processes, i.e., polymorphonuclear neutrophil (PMN) activation, macrophage activation, and lymphocyte recruitment and activation," Dr. Tseng explained. "In abnormal adult wound healing, the PMN lifespan is prolonged, and the macrophages become M1 cells, which delay phagocytosis of the apoptotic neutrophils. When macrophages are activated, adaptive immunity takes over to drive inflammation further aggravated by lymphocytic activation. This triggers persistent inflammation, scarring, or a non-healing state."

Use of cryopreserved amniotic membranes has been shown to affect each of the previously mentioned processes by promoting PMN apoptosis, changing M1 to M2 cells to promote phagocytosis, and suppressing T-cell activation, he noted.

Dr. Tseng and colleagues have reported that the degree of apoptosis of M1 macrophages is highly promoted compared with controls by cryopreserved amniotic membrane. (Li et al., Experimental Eye Research. 2006;82:282-292).

They also identified a complex, HC-HA complex, during the purification of cryopreserved amniotic membrane tissue. The complex is formed between hyaluronic acid (HA) and a peptide called heavy chain (HC) from a serum protein through a covalent ester bond.

"The HC-HA complex is extremely potent in down-regulating the M1 macrophage phenotype and up- regulating the M2 macrophage phenotype," Dr. Tseng said. "This was proven by protein array analysis and additional analysis of the cell phenotype."

In addition to those activities, he also demonstrated that the HC-HA complex is highly potent for promoting phagocytosis of apoptotic neutrophils. HC-HA also can severely inhibit the process by which macrophages become osteoclasts.

In addition, HC-HA can suppress T-cell activation and vascular endothelial cell proliferation in a dose-dependent manner.

"We have obtained some basic research data that explain the molecular activity of cryopreserved amniotic membrane when it is used on the ocular surface and in other parts of the body to modify adult wound healing toward that more resembling the fetal state," Dr. Tseng concluded. "This allows us to begin to appreciate the regenerative process in adults."

FYI

Scheffer C.G. Tseng, MD, PhD
E-mail: stseng@ocularsurface.com

Dr. Tseng has a financial interest in the subject matter. Transplantation of AmnioGraft and AmnioGuard for ocular surface reconstruction and placement of ProKera was approved by the Centers for Medicare and Medicaid Services. Dr. Tseng received grant support from the National Institutes of Health for development of ProKera and development of amniotic membrane powder and purified components against inflammation, scarring, and angiogenesis.