Table 1.

Characteristics and drawbacks of various established and primary RPE cell lines.

Model	Species	Type of cell line	Source	General characteristics and drawbacks	References
ARPE-19	Human	Established	Globes of a 19-year-old male donor who had passed away 2 h before extraction	General characteristics: (i) “Cobblestone appearance” and forms a monolayer (ii) Increasing pigmentation in cells with passages (iii) Formation of domes, indicating ability to pump ions vectorially (iv) Expresses cellular retinaldehyde-binding protein (CRALBP) and RPE-specific protein (RPE65), which are components in the retinoid visual cycle (v) Diploid karyology Drawbacks: (i) Low transepithelial resistance (TER) measurement which could compromise barrier functions (ii) Unable to obtain complete polarization (iii) Heterogenous expression of CRALBP (iv) Varied in pigmentation across different cells (v) Inconsistent formation of microvilli (vi) Deletion in chromosome 8 and addition in chromosome 19 (vii) Features such as morphology, retinoid metabolism, secretion of vascular endothelial growth factor (VEGF), and pigment epithelium-derived factor (PDEF) become compromised with increasing passages	[24, 40, 41]
D407	Human	Established	Globes of a 12-year-old white male	General characteristics: (i) “Cobblestone appearance” and forms a monolayer (ii) Has intercellular junctional complexes linking tightly apposed membranes by N-cadherin (iii) Has cortical microfilaments parallel to the plasma membrane and actin filaments bound to the lateral surface of the cells (iv) Short microvilli on apical surfaces of the cells (v) Contained keratins 7, 8, 18, and 19 and formed the keratin filament network throughout the cytoplasm in confluent cells (vi) Expresses CRALBP, indicating the transport of retinoids (vii) Expresses vimentin, which is commonly expressed in many epithelial cells (viii) Able to subculture for more than 200 times Drawbacks: (i) Lack of pigmentation (ii) Form triploid karyotype when cells are more than 50 passages (iii) Low TER measurement (iv) Did not localize tight junction protein zonula occludens-1 (ZO-1) to cell borders, indicating impairment in barrier function (v) Loss of polarization in spectrin associated with the actin and transmembrane proteins (vi) Only one out of the three enzymatic reactions in the metabolism of vitamin A, retinol dehydrogenase (RDH) activity was observed	[25, 42]
DrRPE	Zebrafish	Primary cell line	Eyes of 15 3-month-old adult zebrafish	General characteristics: (i) Cell diameter is 15-19 μm (ii) Optimum growth condition is at 28°C with 15% FBS (iii) Doubling time is around 40 h (iv) Forms monolayer of majority mononucleate (v) Cells form pigment granules in 10 days (vi) Expresses RPE65 and cytokeratin 19 (vii) Cells were able to be subculture more than 75 times and were able to recover from a year of liquid nitrogen storage even at passage 75 (viii) High plating efficiency (ix) Diploid chromosomes, ranging from 38-53 chromosomes, with 50 chromosomes being the most common number (x) Able to convert all-trans-retinol to retinyl esters, producing retinosomes Drawbacks: (i) Some binucleate cells were found in culture (ii) Loss of melanin granules with increasing passages	[33]
Bovine RPE cells	Bovine	Primary cell line	Globes of freshly slaughtered bovine	General characteristics: (i) Polygonal or cuboidal shaped lightly pigmented cells with round nuclei (ii) Expresses vimentin, S100, and cytokeratin proteins (iii) Has a slower growth rate as compared to the iris pigment epithelium, iris melanocyte, and choroidal melanocyte	[43]