Differential effects of dexamethasone and indomethacin on Tenon's capsule fibroblasts: Implications for glaucoma surgery

<p>The Pro-Fibrotic Behavior of Human Tenon’s Capsule Fibroblasts in Medically Treated Glaucoma Patients</p>

“…18 For this reason, we developed a novel in vitro approach to study the behaviour of HTCFs in a tissue mimetic model. 35 Our BATs are similar to the established fibroblast populated collagen lattice model in that they are appropriate for measuring fibroblast-collagen interactions. 36 However, AA2P, which is vitamin C that is required for collagen metabolism, 31 Figure 2 Comparing the ratio of the amount of alpha-smooth muscle actin (αSMA) to number of HTCFs.…”

“…HTCFs are known to be essential in the postoperative wound healing and scarring response following GFS. 35 Therefore, they have been used extensively in experiments to outline this wound healing response and test potential therapeutic interventions to modulate fibrosis. 53,54 Using a BAT model, we demonstrated differing fibrogenic properties of HTCFs collected from patients medically treated for glaucoma compared to HTCFs isolated from patients not treated for glaucoma.…”

A Tenon’s capsule/bulbar conjunctiva interface biomimetic to model fibrosis and local drug delivery

“…Intraoperative drug delivery is one of the key ways of preventing and treating ocular fibrosis, yet in vitro models for local drug delivery within tissue-like structures are lacking. Fibroblast-populated collagen lattices have long been used as a surrogate model for tissue contraction to screen potential anti-scarring treatments [ 32 ], especially in the context of preventing post-surgical scarring after glaucoma filtration surgery [ 12 , 33 , 34 ], using bulbar conjunctiva and/or Tenon’s capsule fibroblasts [ 1 , 35 , 36 ]. However, these have been of limited use to the development of less toxic anti-scarring drugs and/or new delivery systems, as the soft, loose gels do not suitably mimic human tissue composition and stiffness, and are not readily amenable to incorporation of slow release drug delivery devices.…”

“…focusing on fibrotic environments using fibrotic fibroblasts, or on the role of inflammation by varying macrophage numbers). This would be particularly useful for studying the effect of anti-inflammatory drugs, which are currently used postoperatively to further reduce the risk of scarring and surgical failure, or pre-operatively to minimise the amount of anti-metabolite used to diminish the risk of complications [ 1 , 35 ]. Such drugs (steroids, NSAIDs) have been shown to have effects on Tenon’s fibroblasts, for example in classical collagen contraction models [ 35 ], and understanding their effect on the resident cells of the conjunctiva/Tenon’s capsule (fibroblasts/inflammatory cells) will inform and refine the use of perioperative anti-inflammatory treatments.…”

“…This would be particularly useful for studying the effect of anti-inflammatory drugs, which are currently used postoperatively to further reduce the risk of scarring and surgical failure, or pre-operatively to minimise the amount of anti-metabolite used to diminish the risk of complications [ 1 , 35 ]. Such drugs (steroids, NSAIDs) have been shown to have effects on Tenon’s fibroblasts, for example in classical collagen contraction models [ 35 ], and understanding their effect on the resident cells of the conjunctiva/Tenon’s capsule (fibroblasts/inflammatory cells) will inform and refine the use of perioperative anti-inflammatory treatments. In addition, because potential anti-scarring drugs can be inserted fully within the 3D tissue-like environment, as it would be in patients, it represents a unique system to evaluate local drug delivery designs and their effects on the conjunctiva cellular components.…”