@article{mowat_hash_mzyk_harned_nagar_mcgahan_2016, title={Evaluation of the proliferative capacity of canine retinal pigment epithelial cells harvested from different regions of the fundus}, volume={57}, number={12}, journal={Investigative Ophthalmology and Visual Science}, author={Mowat, F. M. and Hash, J. and Mzyk, P. and Harned, J. and Nagar, S. and McGahan, M. C.}, year={2016} }
 @article{harned_nagar_mcgahan_2014, title={Hypoxia controls iron metabolism and glutamate secretion in retinal pigmented epithelial cells}, volume={1840}, ISSN={["1872-8006"]}, DOI={10.1016/j.bbagen.2014.06.012}, abstractNote={Blood-barrier systems are essential in controlling iron levels in organs such as the brain and eye, both of which experience hypoxia in pathological conditions. While hypoxia's effects on numerous iron regulatory and storage proteins have been studied, little is known about how hypoxia affects iron metabolism. Iron also controls glutamate production and secretion; therefore the effects of hypoxia on iron metabolism and glutamate secretion were studied in polarized retinal pigmented epithelial (RPE) cells. Primary canine RPE were cultured in Millicells to create polarized cell cultures. Iron uptake and efflux were measured in hypoxic and normoxic conditions. RPE were loaded with 59Fe-transferrin. Glutamate concentrations in the cell conditioned media were also measured. Hypoxia induced a large increase in iron efflux from RPE in the basolateral direction. Glutamate secretion occurred mainly in the basolateral direction which is away from the retina and out of the eye in vivo. Glutamate secretion was doubled under hypoxic conditions. Hypoxia is known to induce oxidative damage. The current results show that iron, a key catalyst of free radical generation, is removed from RPE under hypoxic conditions which may help protect RPE from oxidative stress. Results obtained here indicate the importance of using polarized tight junctional cells as more physiologically relevant models for blood-barrier-like systems. While the effects of hypoxia on iron efflux and glutamate secretion may be protective for RPE cells and retina, increased glutamate secretion in the brain could cause some of the damaging neurological effects seen in stroke.}, number={10}, journal={BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS}, author={Harned, Jill and Nagar, Steven and McGahan, M. Christine}, year={2014}, month={Oct}, pages={3138–3144} }
 @article{lall_harned_mcgahan_2013, title={Hydrogen peroxide and extracellular signal-related kinase 1/2 pathway regulate ferritin levels in retinal pigmented and lens epithelial cells}, volume={19}, journal={Molecular Vision}, author={Lall, M. M. and Harned, J. and McGahan, M. C.}, year={2013}, pages={2106–2112} }
 @article{harned_ferrell_nagar_goralska_fleisher_mcgahan_2012, title={Ceruloplasmin alters intracellular iron regulated proteins and pathways: Ferritin, transferrin receptor, glutamate and hypoxia-inducible factor-1α}, volume={97}, ISSN={0014-4835}, url={http://dx.doi.org/10.1016/j.exer.2012.02.001}, DOI={10.1016/j.exer.2012.02.001}, abstractNote={Ceruloplasmin (Cp) is a ferroxidase important to the regulation of both systemic and intracellular iron levels. Cp has a critical role in iron metabolism in the brain and retina as shown in patients with aceruloplasminemia and in Cp−/−hep−/y mice where iron accumulates and neural and retinal degeneration ensue. We have previously shown that cultured lens epithelial cells (LEC) secrete Cp. The purpose of the current study was to determine if cultured retinal pigmented epithelial cells (RPE) also secrete Cp. In addition, the effects of exogenously added Cp on iron regulated proteins and pathways, ferritin, transferrin receptor, glutamate secretion and levels of hypoxia-inducible factor-1α in the nucleus were determined. Like LEC, RPE secrete Cp. Cp was found diffusely distributed within both cultured LEC and RPE, but the cell membranes had more intense staining. Exogenously added Cp caused an increase in ferritin levels in both cell types and increased secretion of glutamate. The Cp-induced increase in glutamate secretion was inhibited by both the aconitase inhibitor oxalomalic acid as well as iron chelators. As predicted by the canonical view of the iron regulatory protein (IRP) as the predominant controller of cellular iron status these results indicate that there is an increase in available iron (called the labile iron pool (LIP)) in the cytoplasm. However, both transferrin receptor (TfR) and nuclear levels of HIF-1α were increased and these results point to a decrease in available iron. Such confounding results have been found in other systems and indicate that there is a much more complex regulation of intracellularly available iron (LIP) and its downstream effects on cell metabolism. Importantly, the Cp increased production and secretion of the neurotransmitter, glutamate, is a substantive finding of clinical relevance because of the neural and retinal degeneration found in aceruloplasminemia patients. This finding and Cp-induced nuclear translocation of the hypoxia-inducible factor-1 (HIF1) subunit HIF-1α adds novel information to the list of critical pathways impacted by Cp.}, number={1}, journal={Experimental Eye Research}, publisher={Elsevier BV}, author={Harned, J. and Ferrell, J. and Nagar, S. and Goralska, M. and Fleisher, L.N. and McGahan, M.C.}, year={2012}, month={Apr}, pages={90–97} }
 @article{harned_ferrell_lall_fleisher_nagar_goralska_mcgahan_2010, title={Altered Ferritin Subunit Composition: Change in Iron Metabolism in Lens Epithelial Cells and Downstream Effects on Glutathione Levels and VEGF Secretion}, volume={51}, ISSN={["1552-5783"]}, DOI={10.1167/iovs.09-3861}, abstractNote={PURPOSE
The iron storage protein ferritin is necessary for the safe storage of iron and for protection against the production of iron-catalyzed oxidative damage. Ferritin is composed of 24 subunits of two types: heavy (H) and light (L). The ratio of these subunits is tissue specific, and alteration of this ratio can have profound effects on iron storage and availability. In the present study, siRNA for each of the chains was used to alter the ferritin H:L chain ratio and to determine the effect of these changes on ferritin synthesis, iron metabolism, and downstream effects on iron-responsive pathways in canine lens epithelial cells.


METHODS
Primary cultures of canine lens epithelial cells were used. The cells were transfected with custom-made siRNA for canine ferritin H- and L-chains. De novo ferritin synthesis was determined by labeling newly synthesized ferritin chains with 35S-methionine, immunoprecipitation, and separation by SDS-PAGE. Iron uptake into cells and incorporation into ferritin was measured by incubating the cells with 59Fe-labeled transferrin. Western blot analysis was used to determine the presence of transferrin receptor, and ELISA was used to determine total ferritin concentration. Ferritin localization in the cells was determined by immunofluorescence labeling. VEGF, glutathione secretion levels, and cystine uptake were measured.


RESULTS
FHsiRNA decreased ferritin H-chain synthesis, but doubled ferritin L-chain synthesis. FLsiRNA decreased both ferritin H- and L-chain synthesis. The degradation of ferritin H-chain was blocked by both siRNAs, whereas only FHsiRNA blocked the degradation of ferritin L-chain, which caused significant accumulation of ferritin L-chain in the cells. This excess ferritin L-chain was found in inclusion bodies, some of which were co-localized with lysosomes. Iron storage in ferritin was greatly reduced by FHsiRNA, resulting in increased iron availability, as noted by a decrease in transferrin receptor levels and iron uptake from transferrin. Increased iron availability also increased cystine uptake and glutathione concentration and decreased nuclear translocation of hypoxia-inducible factor 1-alpha and vascular endothelial growth factor (VEGF) accumulation in the cell-conditioned medium.


CONCLUSIONS
Most of the effects of altering the ferritin H:L ratio with the specific siRNAs were due to changes in the availability of iron in a labile pool. They caused significant changes in iron uptake and storage, the rate of ferritin synthesis and degradation, the secretion of VEGF, and the levels of glutathione in cultured lens epithelial cells. These profound effects clearly demonstrate that maintenance of a specific H:L ratio is part of a basic cellular homeostatic mechanism.}, number={9}, journal={INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE}, author={Harned, Jill and Ferrell, Jenny and Lall, Marilyn M. and Fleisher, Lloyd N. and Nagar, Steven and Goralska, Malgorzata and McGahan, M. Christine}, year={2010}, month={Sep}, pages={4437–4446} }
 @article{goralska_ferrell_harned_lall_nagar_fleisher_mcgahan_2009, title={Iron metabolism in the eye: A review}, volume={88}, ISSN={0014-4835}, url={http://dx.doi.org/10.1016/j.exer.2008.10.026}, DOI={10.1016/j.exer.2008.10.026}, abstractNote={This review article covers all aspects of iron metabolism, which include studies of iron levels within the eye and the processes used to maintain normal levels of iron in ocular tissues. In addition, the involvement of iron in ocular pathology is explored. In each section there is a short introduction to a specific metabolic process responsible for iron homeostasis, which for the most part has been studied in non-ocular tissues. This is followed by a summary of our current knowledge of the process in ocular tissues.}, number={2}, journal={Experimental Eye Research}, publisher={Elsevier BV}, author={Goralska, M. and Ferrell, J. and Harned, J. and Lall, M. and Nagar, S. and Fleisher, L.N. and McGahan, M.C.}, year={2009}, month={Feb}, pages={204–215} }
 @article{harned_fleisher_mcgahan_2006, title={Lens epithelial cells synthesize and secrete ceruloplasmin: Effects of ceruloplasmin and transferrin on iron efflux and intracellular iron dynamics}, volume={83}, ISSN={["0014-4835"]}, DOI={10.1016/j.exer.2006.01.018}, abstractNote={Although an essential nutrient, iron can catalyze damaging free radical reactions. Therefore elaborate mechanisms have evolved to carefully regulate iron metabolism. Ceruloplasmin, a protein with ferroxidase activity, and transferrin, an iron binding protein have important roles in maintaining iron homeostasis in cells. Since oxidative damage is a hallmark of cataractogenesis, it is essential to determine iron's role in lenticular physiology and pathology. In the current study of lens epithelial cells, the effects of ceruloplasmin and transferrin on intracellular distribution and efflux of iron were determined. Both ceruloplasmin and transferrin increased iron efflux from these cells and their effects were additive. Ceruloplasmin had significant effects on extracellular iron distribution only in cases of iron overload. Surprisingly, both transferrin and ceruloplasmin had significant effects on intracellular iron distribution. Under physiological conditions, ceruloplasmin increased iron incorporation into the storage protein, ferritin. Under conditions of iron overload, it decreased iron incorporation into ferritin, which is consistent with increased efflux of iron. Measurements of an intracellular chelatable iron pool indicated that both transferrin and ceruloplasmin increased the size of this pool at 24 h, but these increases had different downstream effects. Finally, lens epithelial cells made and secreted transferrin and ceruloplasmin. These results indicate an important role for these proteins in iron metabolism in the lens.}, number={4}, journal={EXPERIMENTAL EYE RESEARCH}, author={Harned, J. and Fleisher, L. N. and McGahan, M. C.}, year={2006}, month={Oct}, pages={721–727} }
 @article{mcgahan_harned_mukunnemkeril_goralska_fleisher_ferrell_2005, title={Iron alters glutamate secretion by regulating cytosolic aconitase activity}, volume={288}, ISSN={["1522-1563"]}, DOI={10.1152/ajpcell.00444.2004}, abstractNote={Glutamate has many important physiological functions, including its role as a neurotransmitter in the retina and the central nervous system. We have made the novel observations that retinal pigment epithelial cells underlying and intimately interacting with the retina secrete glutamate and that this secretion is significantly affected by iron. In addition, iron increased secretion of glutamate in cultured lens and neuronal cells, indicating that this may be a common mechanism for the regulation of glutamate production in many cell types. The activity of the iron-dependent enzyme cytosolic aconitase (c-aconitase) is increased by iron. The conversion of citrate to isocitrate by c-aconitase is the first step in a three-step process leading to glutamate formation. In the present study, iron increased c-aconitase activity, and this increase was associated with an increase in glutamate secretion. Inhibition of c-aconitase by oxalomalate decreased glutamate secretion and completely inhibited the iron-induced increase in glutamate secretion. Derangements in both glutamate secretion and iron metabolism have been noted in neurological diseases and retinal degeneration. Our results are the first to provide a functional link between these two physiologically important substances by demonstrating a significant role for iron in the regulation of glutamate production and secretion in mammalian cells resulting from iron regulation of aconitase activity. Glutamatergic systems are found in many nonneuronal tissues. We provide the first evidence that, in addition to secreting glutamate, retinal pigment epithelial cells express the vesicular glutamate transporter VGLUT1 and that regulated vesicular release of glutamate from these cells can be inhibited by riluzole.}, number={5}, journal={AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY}, author={McGahan, MC and Harned, J and Mukunnemkeril, M and Goralska, M and Fleisher, L and Ferrell, JB}, year={2005}, month={May}, pages={C1117–C1124} }
 @article{harned_grimes_mcgahan_2003, title={The effect of UVB irradiation on ferritin subunit synthesis, ferritin assembly and Fe metabolism in cultured canine lens epithelial cells}, volume={77}, ISSN={["0031-8655"]}, DOI={10.1562/0031-8655(2003)077<0440:TEOUIO>2.0.CO;2}, abstractNote={Abstract Ferritin is a multimeric protein consisting of heavy and light chains assembled in different tissue-specific ratios, which can protect cells from oxidative stress by storing reactive iron (Fe). Because the lens is constantly exposed to UV irradiation, we studied its effects on ferritin synthesis and Fe metabolism in cultured lens epithelial cells with and without ascorbic acid (Asc). UVB caused a large increase in accumulation of newly synthesized ferritin chains; this increase was additive to that induced by Asc. In contrast to the Asc-induced increase in Fe storage, Fe storage in ferritin was unaltered by UVB. Although UVB increased accumulation of newly synthesized ferritin chains, total ferritin levels were unaltered. In contrast, Asc, which induced a quantitatively similar increase in accumulation of newly synthesized ferritin chains, doubled the total amount of ferritin. Because UVB did not change Fe storage in ferritin or the size of the labile Fe pool, it was hypothesized and then determined that these newly synthesized chains did not assemble into functional holoferritin. Numerous studies detail the effects of various treatments on de novo ferritin synthesis; however, this study provides a cautionary note regarding the conclusions of such studies in the absence of data indicating assembly of functional ferritin molecules.}, number={4}, journal={PHOTOCHEMISTRY AND PHOTOBIOLOGY}, author={Harned, J and Grimes, AM and McGahan, MC}, year={2003}, month={Apr}, pages={440–445} }
 @article{goralska_harned_fleisher_mcgahan_1998, title={The effect of ascorbic acid and ferric ammonium citrate on iron uptake and storage in lens epithelial cells}, volume={66}, ISSN={["0014-4835"]}, DOI={10.1006/exer.1997.0466}, abstractNote={Ferritin is the major intracellular iron storage protein which has been shown to protect cells against oxidative damage. Recent reports that an inherited abnormality in human ferritin synthesis is associated with early bilateral cataracts underscore the importance of understanding ferritin synthesis and iron storage in lens epithelial cells. We previously demonstrated that ascorbic acid greatly increases de novo synthesis of ferritin in lens epithelial cells. The objectives of the present study were to determine: (1) the effects of ascorbic acid and ferric ammonium citrate on iron uptake by canine lens epithelial cells from iron bound to transferrin and from ferric chloride and (2) the incorporation of this element into ferritin. Iron uptake by lens epithelial cells from 59ferric chloride was 20 times higher than from 59iron-transferrin and iron deposition into ferritin was 8-fold higher when 59ferric chloride was the source. Ascorbic acid had a stimulatory effect on iron uptake from transferrin and on incorporation of this element into ferritin. The ascorbic acid-induced increase of iron uptake required de novo protein synthesis but not specifically de novo ferritin biosynthesis. Although ferritin is not directly involved in iron uptake, the level of ferritin protein could control the pool of intracellular iron. The present results indicate that iron homeostasis in lens epithelial cells is affected mainly by changes in apoferritin synthesis, which is greatly stimulated by ascorbic acid, rather than by altering the rate of protein degradation, which is very slow in these cells under all circumstances. Ferric ammonium citrate activates iron uptake from transferrin in a wide range of cell lines by generation of free radicals. Ferric ammonium citrate also increased iron uptake from Tf in lens epithelial cells. Ferric ammonium citrate treated cells incorporated 5 times more iron and deposited 2 times more iron into ferritin than control cells. Increased incorporation of iron into ferritin was due to ferric ammonium citrate-induced stimulation of de novo ferritin synthesis rather than an increased rate of iron deposition into pre-existing ferritin. Ferric ammonium citrate had a different effect on iron uptake from ferric chloride; total iron uptake was not significantly increased while deposition into ferritin was significantly decreased. These results demonstrate that iron homeostasis in lens epithelial cells is regulated by ascorbic acid and by changes in the rate of de novo ferritin synthesis. In addition, the differences in iron uptake from transferrin and ferric chloride and its subsequent incorporation into ferritin suggests that the mechanisms by which iron is incorporated into ferritin are source dependent.}, number={6}, journal={EXPERIMENTAL EYE RESEARCH}, author={Goralska, M and Harned, J and Fleisher, LN and McGahan, MC}, year={1998}, month={Jun}, pages={687–697} }
 @article{davidson_harned_grimes_duncan_wormstone_mcgahan_1998, title={Transferrin in after-cataract and as a survival factor for lens epithelium}, volume={66}, ISSN={["1096-0007"]}, DOI={10.1006/exer.1997.0413}, abstractNote={The Fe-transport protein, transferrin (Tf), is synthesized and secreted by whole lenses and cultured lens epithelial cells. Because of Tf's central role in cell growth and proliferation, its participation in lens cell proliferation following cataract extraction was explored using a rabbit model of after-cataract. Varying amounts of the central anterior lens capsule were removed (0, 35, or 80%) following extraction of the lens. The Tf content of and secretion by after-cataract lens capsular sacs containing regenerated lens tissue was determined ex vivo at 0, 3, 5, 7 and 9 weeks post-surgery. In all cases Tf content of and secretion by the lens sacs was higher than that of their contralateral controls (whole lenses). Tf secretion was up to 5-fold higher and metabolic labeling studies indicated secretion of newly synthesized Tf. The sacs contained up to 10 times the concentration of Tf as the control lenses. Human lens after-cataract capsular bags also secreted Tf. The function of Tf as a survival factor was tested on cultured lens epithelial cells. Cells cultured in serum-free medium had a survival rate of only 20-34% if the medium was changed each day. If the medium was never changed during this period, the survival rate was 43-52%, suggesting secretion of essential growth factors by these cells. Addition of 200 microg ml-1 Tf to the medium during each daily change increased survival to levels attained when the medium was not changed. Addition of Tf antibodies to the culture medium during each daily change decreased cell survival to 14%. Apparently Tf acts as a survival factor for lens epithelia and its synthesis is up-regulated in after-cataract lens sacs. These factors suggest that Tf may play an important role in the pathogenesis of lens epithelial cell proliferation and after-cataract formation following cataract surgery.}, number={2}, journal={EXPERIMENTAL EYE RESEARCH}, author={Davidson, MG and Harned, J and Grimes, AM and Duncan, G and Wormstone, IM and McGahan, MC}, year={1998}, month={Feb}, pages={207–215} }
 @article{goralska_harned_grimes_fleisher_mcgahan_1997, title={Mechanisms by which ascorbic acid increases ferritin levels in cultured lens epithelial cells}, volume={64}, ISSN={["1096-0007"]}, DOI={10.1006/exer.1996.0227}, abstractNote={A previous study demonstrated that ascorbic acid increased the concentration of the iron storage protein, ferritin. In cultured lens epithelial cells. The current study was designed to determine the mechanism by which ascorbic acid exerts this effect. Ascorbic acid increased both ferritin mRNA levels (by about 30%) and translation of ferritin (de novo synthesis was increased up to 15-fold) within 6 hr. Cycloheximide completely abolished the ability of ascorbic acid to increase ferritin levels, whereas actinomycin D only decreased it by about 30%. Therefore, the ascorbic-acid induced increase in ferritin concentration is due mainly to an increase in ferritin synthesis at the translational levels. This is a novel role for ascorbic acid. Addition of iron with ascorbic acid further increased de novo synthesis of ferritin, but this additive effect was only noted at a later time point (20 hr). Factors which decrease ferritin mRNA translation, such as the reducing agent dithiothreitol or the iron chelator desferrioxamine, reduced the ascorbic acid effect on de novo ferritin synthesis. The effects of ascorbic acid on ferritin mRNA levels may be mediated by its oxidation product, H2O2, since, like ascorbic acid, H2O2 increased ferritin mRNA levels by 30%. However, in contrast to the ascorbic acid-induced increase in translation of ferritin, H2O2 substantially decreased de novo ferritin synthesis. This effect of H2O2 could have physiological significance in eyes where concentrations of H2O2 in the aqueous humor are elevated. High levels of H2O2 could decrease the concentration of ferritin within the lens. Since ferritin sequesters iron and has been shown to decrease oxidative damage by limiting the availability of iron to catalyse free radical reactions, H2O2-induced reduction in ferritin concentration in the lens could have deleterious effects. The ability of ascorbic acid to increase ferritin concentration in lens epithelial cells could provide an additional protective mechanism for this antioxidant vitamin. The importance of ferritin to normal lens functioning is underscored by the recent finding that humans with a dominantly inherited abnormality in ferritin synthesis exhibit early bilateral cataracts.}, number={3}, journal={EXPERIMENTAL EYE RESEARCH}, author={Goralska, M and Harned, J and Grimes, AM and Fleisher, LN and McGahan, MC}, year={1997}, month={Mar}, pages={413–421} }
 @article{mcgahan_harned_goralska_sherry_fleisher_1995, title={TRANSFERRIN SECRETION BY LENS EPITHELIAL-CELLS IN CULTURE}, volume={60}, ISSN={["0014-4835"]}, DOI={10.1016/S0014-4835(05)80008-9}, abstractNote={Transferrin (Tf), the plasma iron transport protein which supports cell proliferation and differentiation and has bacteriostatic, antioxidant and anti-inflammatory activity, has been found in relatively high concentrations in the intraocular fluids. Intraocular synthesis of Tf has recently been demonstrated, although the intraocular tissue(s) responsible have not been identified. We designed this study to determine whether certain ocular tissues can make and secrete transferrin. Transferrin content of aqueous and vitreous humors and whole lenses was determined by ELISA. Transferrin secretion by cultured epithelia from lens and ciliary body was also measured. In addition, Northern blots of RNA from cultured lens epithelial cells, ciliary body pigmented and non-pigmented epithelial cells, and from whole iris, ciliary body and retina were probed with riboprobes for Tf mRNA and 18S rRNA. Transferrin made up 23% and 16% of total canine aqueous and vitreous protein. All ocular tissues and cultured cells tested contained mRNA for Tf, however Tf was secreted into the bathing medium from lens epithelial cell cultures, but not from either the pigmented or non-pigmented epithelial cells of the ciliary body Cycloheximide inhibited secretion of Tf from the lens epithelial cells. Lenses from inflamed eyes contained higher levels of Tf than their contralateral controls. This is the first experimental demonstration that an intraocular tissue can make and secrete Tf. Transferrin secretion by the lens may contribute significantly to the IOF content of this important intraocular protein.}, number={6}, journal={EXPERIMENTAL EYE RESEARCH}, author={MCGAHAN, MC and HARNED, J and GORALSKA, M and SHERRY, B and FLEISHER, LN}, year={1995}, month={Jun}, pages={667–673} }
 @article{mcgahan_harned_grimes_fleisher_1994, title={REGULATION OF FERRITIN LEVELS IN CULTURED LENS EPITHELIAL-CELLS}, volume={59}, ISSN={["0014-4835"]}, DOI={10.1006/exer.1994.1140}, abstractNote={In most eukaryotic cells, synthesis of the iron storage protein, ferritin is regulated by iron levels and redox conditions. Proper iron storage is important to protect against damaging iron-catalysed free radical reactions. Although iron-catalysed reactions are believed to contribute to oxidative damage and cataractogenesis, little is known about iron storage in the lens. In this study, ferritin concentration was measured in cultured canine lens epithelial cells. Baseline ferritin concentration ranged from 76-163 ng (mg protein)-1; cells cultured in low-iron media had significantly lower ferritin levels than cells cultured in iron-supplemented media. Addition of a large excess of iron as hemin resulted in an eight-fold increase in ferritin concentration. The iron chelator, Desferal, significantly decreased ferritin concentration. The reducing agent dithiothreitol decreased the hemin-induced increase in ferritin levels, but not baseline levels. In contrast, ascorbic acid induced a large increase in ferritin content. Other studies have shown that induction of ferritin synthesis can protect against oxidative damage. Regulation of ferritin levels may represent a mechanism by which the lens epithelium is protected from oxidative damage. In vivo, epithelial cells are normally exposed to much lower iron concentrations than the cultured lens epithelial cells in this study. However, in pathological circumstances, the iron content and redox state of the aqueous humor is dramatically altered and may affect the steady state levels of ferritin within the lens. This remains to be determined.}, number={5}, journal={EXPERIMENTAL EYE RESEARCH}, author={MCGAHAN, MC and HARNED, J and GRIMES, AM and FLEISHER, LN}, year={1994}, month={Nov}, pages={551–555} }