Table 1 of
Hayat, Mol Vis 2025; 31:463-484. Table 1 of
Hayat, Mol Vis 2025; 31:463-484.
Table 1. Summary of epidemiologic and molecular studies on proteostasis-related markers in pseudoexfoliation syndrome (PEXS) and pseudoexfoliation glaucoma (PEXG).
| Proteostatic markers | Study specimen | Sample size* | Role in PEX pathogenesis | References | ||
|---|---|---|---|---|---|---|
| Clusterin (CLU) | Cornea, Trabecular Meshwork, iris, lens, ciliary processes, aqueous humor (AH) | 20 PEXS | Clusterin deficiency in anterior segment tissues of PEX eyes; strong binding to PEX deposits and relative increase in AH of PEXG. Deficiency may impair proteostasis and promote PEXM deposition. | Zenkel et al., 2006 | ||
| 20 PEXG | ||||||
| 28 Controls | ||||||
| Aqueous Humor (AH) | 16 PEXS | Study emphasizes genetic association; higher deposition in LC of PEXG eyes, augmenting extracellular protein accumulation. | Padhy et al., 2014 | |||
| 18 PEXG | ||||||
| 21 Controls | ||||||
| Lens capsule (LC) | 11 PEXS | |||||
| 09 PEXG | ||||||
| 12 Controls | ||||||
| Blood | 19 PEXS | 3′-UTR polymorphisms and promoter hypomethylation jointly dysregulate clusterin, impairing proteostasis in PEXS/PEXG. | Kapuganti et al., 2023b | |||
| 18 PEXG | ||||||
| 20 Controls | ||||||
| Lens capsule | 6 PEXS | |||||
| 3 PEXG | ||||||
| 6 Controls | ||||||
| Heat shock proteins | Ciliary processes and | 6 PEXS | Alterations in cellular cytoprotective mechanisms in anterior segment tissues of PEX eyes. | Zenkel et al., 2007 | ||
| (HSP27, HSP40 and HSP60) | Iris tissue | 6 PEXG | ||||
| Ubiquitin conjugating enzymes | 6 Controls | |||||
| (UBE2A/2B) | ||||||
| Heat shock factor 1 | Lens capsule | 11 PEXS | An upregulated HSF1 mRNA levels indicate proteotoxic stress in anterior eye tissues of PEXS-affected patients. | Padhy et al., 2017 | ||
| (HSF1) | 10 PEXG | |||||
| 21 Controls | ||||||
| Conjunctiva | 09 PEXS | |||||
| 09 PEXG | ||||||
| 21 Controls | ||||||
| Synoviolin (SYVN1) | Lens capsule | 22 PEXS, 19 PEXG, 31 Controls | PEX is marked by upregulation of ER stress markers, but failure of proteasome degradation leads to impaired proteostasis and apoptotic cell death. | Hayat et al., 2019 | ||
| Calnexin (CANX) | 20 PEXS, 17 PEXG, 28 Controls | |||||
| Proteasome subunits | 08 PEXS, 07 PEXG, 10 Controls | |||||
| (PSMD1 and PSMA5) | ||||||
| Ubiquitin B (UBB) | 11 PEXS, 04 PEXG, 17 Controls | |||||
| HSP40 (DNAJ family members) | 08 PEXS | |||||
| HSP60 (HSPD1) | 06 PEXG | |||||
| Caspase 12 (CASP12) | 14 Controls | |||||
| Eukaryotic translation initiation | ||||||
| factor 2-alpha kinase 3 | ||||||
| (EIF2AK3) | ||||||
| Heat shock protein family A member 1A | Lens capsule | 19 PEXS | Decreased expression of HSP70 correlates with hypermethylation of CpG islands in PEXS individuals. | Hayat et al., 2020 | ||
| (HSPA1A/ HSP70) | 16 PEXG | |||||
| 19 Controls | ||||||
| Aqueous humor | 31 PEXS | HSP70 levels in the aqueous humor of patients with PEXS was found to be higher than those in the controls. | Güler M et al., 2020 | |||
| 30 Controls | ||||||
| VCP-interacting membrane protein (VIMP) | Peripheral blood | 17 PEXS | Downregulation of UPR genes across all stages of PEX is a key pathogenic driver, linking impaired proteostasis with progression to glaucoma. | Rao et al., 2020 | ||
| EIF2AK3 (PERK) | mononuclear cells | 11 PEXG | ||||
| Protein disulfide isomerase A3 (PDIA3) | (PBMCs) | 11 Controls | ||||
| Glucosidase II alpha subunit (GANAB) | ||||||
| PTEN-induced kinase 1 (PINK1) | Anterior capsule | 19 PEXS | Findings support the concept that impaired but activated mitophagy is a key pathogenic mechanism in PEX progression. | Dilara et al., 2025 | ||
| Parkin | lens epithelial cells | 20 Controls | ||||
| SQSTM1 (p62) | ||||||
| Microtubule-associated protein | ||||||
| 1A/1B-light chain 3 B (LC3B) | ||||||