Molecular mechanisms and treatments for ocular symblephara

Abstract

There are currently no effective methods to prevent or durably treat ocular symblephara, the adhesions between the palpebral and bulbar conjunctiva. How symblephara form at the molecular level is largely unknown. We present here an overview of current clinical symblephara treatments and describe potential molecular mechanisms behind conjunctival adhesion formation that may inform future symblephara treatment and prevention options. Understanding how symblephara form at the molecular level will facilitate treatment development. Preventative therapies may be possible by targeting symblephara progenitor cells immediately after injuries, while novel therapeutics should be aimed at modulating TGF-β pathways and effector cells in conjunctival scarring to treat symblephara formation more effectively.

Keywords: Conjunctival inflammation; Molecular mechanisms; Preventative therapies; Symblephara; Treatments.

Figure 1:

Symblephara is characterized by band formation between the palpebral and bulbar conjunctiva.

Figure 2:

Representative images showing the different grades of symblephara. A. A representative image of no symblephara present. B. Symblephara grade Ia1+ of the superior fornix caused by alkaline chemical burn. C. Grade Ib0 symblephara following treatment for ocular cicatricial pemphigoid. D. Grade IIb0 medial symblephara following treatment for ocular cicatricial pemphigoid. E. Symblepharon IIb1+ secondary to ocular cicatricial pemphigoid. F. Grade IIb2+ central inferior symblephara of a patient with active ocular cicatricial pemphigoid. G. Symblephara grade IIIc2+ due to Stevens-Johnson Syndrome H. Symblephara grade IVb2+ in a patient with active ocular cicatricial pemphigoid I. Symblephara grade IVc3+ secondary to Stevens-Johnson Syndrome.

Figure 3:

Diagram showing the different cell types that may be involved in symblephara formation including fibroblasts, myofibroblasts, fibrocytes, cell adhesion molecules and immune cells

Figure 4:

Schematic diagram showing the molecular basis of Symblephara. Symblephara may be caused by subconjunctival fibrosis that can be induced due to multiple pathways including the Hippo pathway that has been implicated in fibrosis upregulation. TGF-β is a master regulator of fibrosis. Symblephara may be governed by TGF-β regulation, which may lead to ECM production, decrease in matrix-degrading metalloproteases, integrins and increase in protease inhibitors. TGF-β can in turn be regulated by BMP signaling, which also effects Smad. Future therapies should be aimed at controlling TGF-β signaling either through direct down regulation or through the modulation of fibrosis-forming factors.