Role of interferons in diabetic retinopathy

Table 1 Expression of interferons in samples

Source	Condition of disease	Expression
Tears	DR	(IFN-γ) ↑↑, (IFN-γ/MCP-1) ↓, (IFN-γ/IL-8) ↓[39]
	DNR	(IFN-γ) ↑[39]
Aqueous humor	PDR	(IFN-γ) ↑↑[40]
	NPDR	(IFN-γ) ↑[40]
	DR	(IFN-γ) ↑↑[41], (IFN-α) ↓↓[117,118]
	DNR	(IFN-γ) ↑[41], (IFN-α) ↓[117,118]
Vitreous fluids	DR	(IFN-γ) ↑[42]
	DM	(IFN-γ) ↑[45]
Serum	DR	(IFN-γ) ↑↑[46]
	DNR	(IFN-γ) ↑[46]
	DM	(IFN-γ) ↑[47,48]
Plasma	DM	(IFN-α) ↑, (IFN-β) ↑[113]
Retina	DR	(IFN-β) ↑[115]

DR: Diabetic retinopathy; DNR: Diabetes without retinopathy; PDR: Proliferative diabetic retinopathy; NPDR: Non-proliferative diabetic retinopathy; DM: Diabetes mellitus; IFN: Interferons.

Table 2 Concentration of interferons in patient samples

IIFNs	Source	Condition of disease	Concentration
IFN-γ	Tears (multiplex bead analysis)	Controls	1463.0 ± 158.8 (pg/mL)[39]
		DNR	1612.8 ± 228.2 (pg/mL)[39]
		DR	1957.50 ± 166.1 (pg/mL)[39]
	Aqueous humor (CBA)	Controls	60.29 ± 14.17 (pg/L)[40]
		DNR	54.96 ± 16.29 (pg/L)[40]
		NPDR	114.26 ± 50.76 (pg/L)[40]
		PDR	136.36 ± 35.55 (pg/L)[40]
	Vitreous fluids (ELISA)	Controls	3.83 ± 0.80 (pg/mL)[42]
		DR	6.25 ± 0.84 (pg/mL)[42]
	Serum (ELISA)	Controls	2.9 (pg/mL)[46]
		DNR	27.8 (pg/mL)[46]
		DR	56.8 (pg/mL)[46]
IFN-α	Aqueous humor (Bio-Plex protm magnetic color-bead-based multiplex assay)	Controls	26.2 (0-84) (pg/mL)[117]
		DNR	0 (0-20) (pg/mL)[117]
		DR	0 (0-18) (pg/mL)[117]

Data are expressed as the mean ± SEM or median (range). DNR: Diabetes without retinopathy; DR: Diabetic retinopathy; NPDR: Non-proliferative diabetic retinopathy; PDR: Proliferative diabetic retinopathy; CBA: Cytometric bead array technique; ELISA: Enzyme linked immunosorbent assay; IFN: Interferons.

Table 3 Applications of interferon-α in ocular disorders

IFN	Clinical applications
IFN-α-2a	Ocular surface diseases: Tumors (such as limbal conjunctival melanoma, squamous neoplasias, and conjunctival MALT lymphoma)[134,137]; Mooren’s ulcers[138]; herpes simplex keratitis[139]
	Uveal disease: Behcet's uveitis[131]; serpiginous choroiditis[140]; choroidal neovascularization[141]; HHV-8-associated uveitis[142]; chronic noninfectious posterior uveitis[143]
	Macular and retinal disorders: Uveitic CME; angiogenesis after PRP; refractory non-infectious inflammatory macular edema[144]
IFN-α-2b	Ocular surface diseases: Tumors (such as squamous cell carcinoma[145], melanocytic tumors[145], CIN[146], conjunctival papillomatosis[147], and MALT lymphoma[57]); LSCD[135]; vernal keratoconjunctivitis[132]
	Uveal disease: Metastatic uveal melanoma[148]; Behcet's uveitis[149]
	Macular and retinal disorders: CME caused by intraocular infection[150]; refractory diabetic macular edema[133]
IFN-α-2	Dendritic keratitis[151]

MALT: Mucosa-associated lymphoid tissue; HHV-8: Human herpes virus 8; CME: Cystoid macular edema; PRP: Panretinal photocoagulation; CIN: Conjunctival and corneal intraepithelial neoplasia; LSCD: Limbal stem cell deficiency; IFN: Interferons.