Table 1.
Overview of the results of all the studies included in the review.
| Study | Glaucoma (n) | Control (n) | Age of glaucoma patients (mean ± SD) | Biochemical method | Sampling sites | Markers | Cellular localization | Results |
|---|---|---|---|---|---|---|---|---|
| Hernandez et al. 1994 | 7 | 9 | N/A | ISH and RT-PCR | ONH | Collagen type IV | Astrocytes | ↑ in the LC sections and produced by astrocyte |
| Neufeld et al. 1997 | 8 | 6 | 79±12.3 | IHC | ONH | COX-1 and COX-2 | Astrocytes | ↑COX-1 in astrocytes; Faint COX-2 staining |
| Pena et al. 1999 | 15 | 11 | 76.1±12.6 | IF | ONH | Tenascin C | Astrocytes | ↑ of Tenascin in ON, LC, and post-lamina region |
| Yuan et al. 2000 | 20 | 20 | 79±14 | IHC | ONH | TNF-a and TNF-a receptor 1 | Astrocytes | ↑ TNF-a and TNFR1 parallel to the disease progression |
| Yan et al. 2000 | 11 | 4 | 78.5±5.05 | IHC | ONH | MMPs, TNF-α, and TNF-α receptor 1 | Glial cells | ↑ the intensity of staining and the number of glial cells. |
| Tezel et al. 2000 | 6 | 6 | 72.25±10.8 | IHC | ONH and Retina | HSP 60 and 27 | Astrocytes and RGCs | ↑ HSP 60: RGCs and photoreceptors. HSP27: NFL, RGCs, and retinal vessels |
| Tezel et al. 2001 | 20 | 20 | 78±9 | IHC | Retina | TNF-a and TNF-a receptor 1 | Astrocytes and RGCs | ↑ TNF-a in glial cells and TNF-R1 in the RGCs |
| Yang et al. 2001 | 6 | 6 | 69.2±14.93 | IHC | LC-cross sections | HLA-DR | Astrocytes | ↑HLA-DR expression; localised with GFAP positive cells |
| Yuan et al. 2001 | 20 | 20 | 79 ±17 | IHC | ONH | TGF-B1, B2, TNF-α, TNF-R1, COX-1, COX-2, NOS-2, c-fms, MMP-1. MMP-2, MMP-3, MMP14, TIMP1, TIMP2. TSP, CD68, PCNA, HSP27 | Microglia | Activated microglia with ↑ in TGF-β2, TNF-α, TNF-R1, COX-1, COX-2, NOS-2, c-fms, MMP-1, TIMP-1, TIMP-2, TSP, CD68, PCNA |
| Surgucheva et al. 2002 | 4 | 6 | 68.25±4.92 | IHC | ON | Synucleins | Glial cells | ↑ γ-synuclein in a subset of glial cells in the LC and post-LC regions |
| Tezel et al. 2003 | 30 | 20 | 80.33±8.98 | IHC | Retina | phosphorylated MAPKs | Micro and Macroglia | ↑ in p-ERK in glial cells and ↑ p-JNK and p-38 in the RCG layer. |
| Tezel et al. 2004 | 28 | 20 | 80.4±9.3 | IHC | ONH and retina | HIF-1a | RGC and glial cells | ↑ HIF-1a in glial cells and RGCs; parallel to the visual defect |
| Wang et al. 2006 | 16 | 10 | 82.7 ± 9.3 | IHC | ONH | Endothelin B receptor | Astrocytes | ↑ ETbR in astrocytic processes |
| Tezel et al. 2007 | 38 | 30 | 76.84±11.06 | IHC | ONH and Retina | AGE and RAGE | Astrocytes | ↑ extracellular accumulation of AGEs and localization of RAGEs to RGCs and footplates of the Müller cells |
| Rudzinski et al. 2008 | 8 | 8 | N/A | RT-PCR and IHC | ONH | VEGF, PDGF and collagen XVIII | Astrocytes | ↓VEGF-C and PDGF-A in LC and ↑collagen XVIII and ADAMTSL-3 in LC. |
| Felichenfeld et al. 2008 | 5 | 4 | 77±9 | IHC | ONH | Nitrotyrosine | Astrocytes | ↑ Nitrotyrosine in the pre-laminar ONH blood vessels and glial tissue surrounding the pre-laminar ONH |
| Luo et al. 2010 | 10 | 10 | 84.7 ± 8 | IHC and LC-MS/MS | Retina | TLR-2, 3 and 4 | Astrocytes and Microglia | LC-MS/MS showed ↑ TLR signalling localised to astrocytes and microglia. |
| Tezel et al. 2010 | 38 | 30 | 76.8 ± 11 | LC-MS and IHC | Retina | CFH, CD35, and CD59. | Whole tissues | Immunolabeling of the complement components and the membrane complex in ILs, including the RGCs and IPLs with regional |
| Yang et al. 2011 | 38 | 30 | 76.8 ± 11 | LC-MS/MS, IHC, and WB | Retina | TNF-a and TNF-a receptor 1 | Astrocytes and RGCs | ↑ TNFR1-related downstream proteins, regulators of TNFR1 signalling, and TNFAIP3 were upregulated. |
| Mizokami et al. 2011 | 1 | 1 | N/A | IHC | ONH | AQP-9 and AQP-4 | Glial cells | ↑AQP9 co-localized in the glial cells; no change in the AQP4 expression levels |
| Kerr et al. 2011 | 2 | 3 | 78± 11.3 | IHC | ONH and retina | Connexin43 | Astrocytes | ↑ Connexin43 localized in the LC and near blood vessels and the RGC layer |
| Reszec et al. 2012 | 42 | 2 | N/A | IHC | ONH and retina | HIF-1a | Whole tissue | ↑ HIF-1a in ON RGCs at the perinuclear and cytoplasmic granular regions. |
| Goldhagen et al. 2012 | 10 | 10 | 76.5±6.34 | IHC | ONH | RhoA, ROCK-1, and ROCK-2 | Whole tissue | ↑ RhoA, ROCK-1, and ROCK-2 in the ONH localised to prelaminar and laminar regions |
| Gramlich et al. 2013 | 6 | 9 | N/A | IF | Retina | IgG accumulation | Whole tissue | IgG deposition in the glaucomatous retina and CD3+/IgG+ plasma cells detected |
| Funke et al. 2016 | 4 | 4 | 86±9 | LC-MS/MS and IHC for validation | Retina | ANT3, MeCp2, DFS70 | Whole tissue | LC-MS/MS based analysis of proteome alterations in glaucoma. |
| Margeta et al. 2018 | 13 | 12 | 79.39±12.90 | IHC | ON | CD163 and CD68 for macrophage infiltration | Macrophages | CD163+ macrophages infiltrated the ONH in glaucoma |
| Belmares et al. 2018 | 12 | 12 | N/A | Chemical staining and IF | ONH and TM | Collagen, elastin, Galectin and TGFB2RII | Whole tissue | ↑ in elastin, collagen staining in the glaucomatous ONH. Elastin fibres showed thickening and curling in the LC collagen matrix. ↑ in Galectin and TGFB2II expression glaucomatous ONH, MTZ |
| Chauhan et al. 2019 | 12 | 11 | 70.3 ± 10.5 | IHC, lipidomics | ONH | GBA, GBA2, ASAH1, and ASAH2 | Whole tissue | ↑ in glucosyl sphingosine in glaucoma and mirrored changes in GBA, GBA2, ASAH1, and ASAH2 |
| Guan et al. 2022 | 27 | 19 | 75.8 ± 8.0 | IHC | LC-cross sections | F-actin and GFAP | Astrocytes and Microglia | ↓ GFAP and F-actin area fraction in glaucoma patients. ISH showed the presence of astrocytes and microglia |
| Neufeld 1999 | 11 | 6 | 63 ± 10 | IHC | ONH | HLA-DR and CD45 | Astrocytes and Microglia | Quiescent microglia were Stellate cells with thin, ramified processes, positive for HLA-DR and CD45 but GFAP negative, while activated cells were ameboid, larger, and clustered in compressed LC |
| Neufeld et al. 1997 | 12 | 14 | 74 | IHC | ONH | NOS-1, NOS-2, and NOS-3 | Astrocytes | NOS-1: prelaminar region, LC, and inside the diminished nerve fibre bundles. NOS-2: few cells in the disorganized LC. NOS-3: astrocytes and in the vascular endothelia of large and small vessels |
| Wang et al. 2002 | 10 | 7 | 87.1 ± 6.9 | IHC | Retina | GFAP | Glial cells | Increased density of glial cells with deformed end feet in the peripapillary region. The glial cells were activated in the glaucomatous samples |
Abbreviations: ISH: insitu hybridisation; RT-PCR: Reverse transcription Polymerase Chain Reaction, IHC: Immunohistochemistry, LC-MS/MS: Liquid-chromatography coupled mass-spectrometry, WB: Western Blot, IF: Immunofluorescence, ONH: optic nerve head, COX: cyclooxygenase, TNF: tumor necrosis factor, MMP: Matrix metalloproteinase, HSP: heat shock protein, TGF: transforming growth factor, NOS-2: nitric oxide synthase -2, c-fms: Colony-stimulating factor-1 receptor, TIMP: tissue inhibitor of metalloproteinases, TSP: thrombospondin, CD: Cluster of differentiation, PCNA: proliferating cell nuclear antigen, HLA-DR: human leukocyte antigen-DR subtype, HIF-1a: Hypoxia-inducible factor 1-alpha, MAPKs: Mitogen-activated protein kinases, AGEs: Advanced Glycation End Products, RAGE: receptor for advanced glycation end products, VEGF: Vascular endothelial growth factor, PDGF: Platelet-derived growth factor, TLR: Toll-like receptor, CFH: Complement factor H, AQP: Aquaporin, RhoA: Ras homolog family member A, ROCK: Rho-associated protein kinase, IgG: Immunoglobulin G, ANT3: ADP/ATP translocase 3, MeCp2: methyl-CpG-binding protein 2, DFS70: SRFS1-interacting protein 1, GBA: glucocerebrosidase, ASAH: acylsphingosine amidohydrolase, GFAP: Glial fibrillary acidic protein, LC: lamina cribrosa, RGC: retinal ganglion cells, NFL: Nerve fibre layer, IPL: inner plexiform layer