Developing novel anti-fibrotic therapeutics to modulate post-surgical wound healing in glaucoma: big potential for small molecules

Figures & data

Figure 1. The general phases of wound healing.

Table 1. Summary of properties of different therapeutic molecules in ocular fibrosis.

Therapeutic molecule	Size	Specificity	Tested drug delivery route	Duration of action	Toxicity (potential side effects)
Antibody	10^–9 m	High	Subconjunctival Intracameral	>30 days (end of study)	Low (immunogenic)
siRNA	20–25 base pairs	High	Subconjunctival Intravitreal	>14 days (end of study)	Low (off-target effect, immunogenic)
miRNA	21–25 nucleotides	High	Locked nucleic acid	Decreases fibroblast activity (in vitro)	Low
Viral vector	10^-9 m	High	Subconjunctival Intravitreal	>30 days (end of study)	Moderate (oncogenic, immunogenic)
Nanoparticle	10^–9 m	Moderate	Topical Subconjunctival Intravitreal	>42 days (end of study)	Low (cytotoxic, genotoxic)
Liposome	10^–6 m	Low	Subconjunctival Intravitreal	>14 days (end of study)	Low
Drug inhibitor	10^–6–10^–9 m	Low	Topical Subconjunctival Intravitreal	>30 days (end of study)	Variable (cytotoxic)
Proteoglycan	10^–3 Da	Low	Subconjunctival Intravitreal	>14 days (end of study)	Low
Dendrimer	10^–9 m	Low	Subconjunctival	28 days (maximal effect)	Low

Table 2. Tested anti-fibrotic gene therapeutic targets in the eye.

Therapeutic target	Cell type	Delivery
Transcription factors
NF-κB	Human Tenon’s fibroblasts	siRNA
E2F	Human Tenon’s fibroblasts	Hemagglutinating virus of Japan
Cell cycle regulators
p53	Human Tenon’s fibroblasts	Recombinant adenovirus
p21	Rabbit Tenon’s fibroblasts	Recombinant adenovirus
Skp2/p27	Rabbit Tenon’s fibroblasts	siRNA
Growth factors
TGF-β	Human corneal fibroblasts	siRNA
Proteins
Keratoepithelin	Human trabecular meshwork cells	shRNA
Myocilin	Human trabecular meshwork cells	shRNA
SPARC	Human Tenon’s fibroblasts	siRNA
Matrix GLA protein	Human trabecular meshwork cells	siRNA
miRNAs
miR-29b	Human Tenon’s fibroblasts	miRNA
miR-29b	Human trabecular meshwork cells	miRNA
Others
Smad7	Human conjunctival fibroblasts	Recombinant adenovirus
p38MAPK	Mouse subconjunctival fibroblasts	Adenovirus
Cytosine deaminase	Rabbit Tenon’s fibroblasts	Recombinant adenovirus

SPARC: Secreted protein, acidic, rich in cysteine.

Figure 2. Schematic diagram summarizing the different therapeutic molecules in ocular fibrosis and their modes of action.