Levels Of αB-crystallin Research Articles

Abnormally Upregulated αB-crystallin Was Highly Coincidental with the Astrogliosis in the Brains of Scrapie-Infected Hamsters and Human Patients with Prion Diseases

αB-crystallin is a member of the small heat shock protein family constitutively presenting in brains at a relatively low level. To address the alteration of αB-crystallin in prion disease, the αB-crystallin levels in the brains of scrapie agent 263 K-infected hamsters were analyzed. The levels of αB-crystallin were remarkably increased in the brains of 263 K-infected hamsters, showing a time-dependent manner along with incubation time. Immunohistochemical (IHC) and immunofluorescent (IFA) assays illustrated more αB-crystallin-positive signals in the regions of the cortex and thalamus containing severe astrogliosis. Double-stained IFA verified that the αB-crystallin signals colocalized with the enlarged glial fibrillary acidic protein-positive astrocytes, but not with neuronal nuclei-positive cells. IHC and IFA of the serial brain sections of infected hamsters showed no colocalization and correlation between PrP(Sc) deposits and αB-crystallin increase. Moreover, increased αB-crystallin deposits were observed in the brain sections of parietal lobe of a sporadic Creutzfeldt-Jakob disease (sCJD) case, parietal lobe and thalamus of a G114V genetic CJD case, and thalamus of a fatal family insomnia (FFI) case, but not in a parietal lobe of FFI where only very mild astrogliosis was addressed. Additionally, the molecular interaction between αB-crystallin and PrP was only observed in the reactions of recombinant proteins purified from Escherichia coli, but not either in that of brain homogenates or in that of the cultured cell lysates expressing human PrP and αB-crystallin. Our data indicate that brain αB-crystallin is abnormally upregulated in various prion diseases, which is coincidental with astrogliosis. Direct interaction between αB-crystallin and PrP seems not to be essential during the pathogenesis of prion infection.

Erratum to: Strength training elevates HSP27, HSP70 and αB-crystallin levels in musculi vastus lateralis and trapezius

Strength training elevates HSP27, HSP70 and alpha B-crystallin levels in musculi vastus lateralis and trapezius (vol 112, pg 1773, 2012) : Correction/Errata

Lamins in development, tissue maintenance and stress

Lamins are nuclear intermediate filament proteins. They provide mechanical stability, organize chromatin and regulate transcription, replication, nuclear assembly and nuclear positioning. Recent studies provide new insights into the role of lamins in development, differentiation and tissue response to mechanical, reactive oxygen species and thermal stresses. These studies also propose the existence of separate filament networks for A- and B-type lamins and identify new roles for the different networks. Furthermore, they show changes in lamin composition in different cell types, propose explanations for the more than 14 distinct human diseases caused by lamin A and lamin C mutations and propose a role for lamin B1 in these diseases.

Beneficial Effects of αB-Crystallin in Spinal Cord Contusion Injury

αB-crystallin is a member of the heat shock protein family that exerts cell protection under several stress-related conditions. Recent studies have revealed that αB-crystallin plays a beneficial role in a mouse model of multiple sclerosis, brain ischemia, and Alexander disease. Whether αB-crystallin plays a role in modulating the secondary damage after CNS trauma is not known. We report here that αB-crystallin mediates protective effects after spinal cord injury. The levels of αB-crystallin are reduced in spinal cord tissue following contusion lesion. In addition, administration of recombinant human αB-crystallin for the first week after contusion injury leads to sustained improvement in locomotor skills and amelioration of secondary tissue damage. We also provide evidence that recombinant human αB-crystallin modulates the inflammatory response in the injured spinal cord, leading to increased infiltration of granulocytes and reduced recruitment of inflammatory macrophages. Furthermore, the delivery of recombinant human αB-crystallin promotes greater locomotor recovery even when the treatment is initiated 6 h after spinal cord injury. Our findings suggest that administration of recombinant human αB-crystallin may be a good therapeutic approach for treating acute spinal cord injury, for which there is currently no effective treatment.

Deficiency of αB crystallin augments ER stress-induced apoptosis by enhancing mitochondrial dysfunction

AbstractEndoplasmic reticulum (ER) stress is linked to several pathological conditions including age-related macular degeneration. Excessive ER stress initiates cell death cascades which are mediated, in part, through mitochondrial dysfunction. Here, we identify αB crystallin as an important regulator of ER stress-induced cell death. Retinal pigment epithelial (RPE) cells from αB crystallin (–/–) mice, and human RPE cells transfected with αB crystallin siRNA, are more vulnerable to ER stress induced by tunicamycin. ER stress-mediated cell death is associated with increased levels of reactive oxygen species, depletion of glutathione in mitochondria, decreased superoxide dismutase activity, increased release of cytochrome c, and activation of caspases 3 and 4. The ER stress signaling inhibitors, salubrinal and 4-(2-aminoethyl) benzenesulfonyl fluoride, decrease mitochondrial damage and reduce RPE apoptosis induced by ER stress. Prolonged ER stress decreases levels of αB crystallin, thus exacerbating mitochondrial dysfunction. Overexpression of αB crystallin protects RPE cells from ER stress-induced apoptosis by attenuating increases in Bax, CHOP, mitochondrial permeability transition, and cleaved caspase 3. Thus, these data collectively demonstrate that αB crystallin provides critical protection of mitochondrial function during ER stress-induced RPE apoptosis.

The role of small heat-shock protein αB-crystalline (HspB5) in COPD pathogenesis

BackgroundαB-crystallin (HspB5) is a chaperone whose role as a marker of innate immunity activation as well as its therapeutic potential have recently been investigated in several inflammatory diseases: multiple sclerosis, myocardial ischemia, and Guillain–Barré syndrome.AimThe aim of this study is to determine the role of αB-crystallin in chronic obstructive pulmonary disease (COPD) pathogenesis and inflammation.MaterialsPlasma levels of αB-crystallin were studied in 163 patients: 52 healthy non-COPD smokers; 20 COPD smokers in Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages I–II; 43 COPD smokers in GOLD stages III-IV. Forty-eight patients were diagnosed with acute inflammatory respiratory disease. The plasma levels of αB-crystallin antibodies were determined by an enzyme-linked immunosorbent assay (Calbiochem), and were confirmed with Western blotting. Tissue expression of the protein was compared in three different groups of patients: COPD smokers, COPD nonsmokers, and in patients with age-related emphysema.ResultsThe mean level of anti-αB-crystallin antibodies in non-COPD smokers was 0.291nm. In COPD smokers it was 0.352 nm and, in patients with inflammatory lung diseases, 0.433 nm. There was a statistically significant difference between COPD smokers and healthy non-COPD smokers (P = 0.010). The same could be observed comparing the group of patients with acute inflammation and non-COPD healthy smokers (P = 0.007). There was no statistically significant difference between patients with mild/moderate inflammation and those with severe COPD. Tissue detection of the protein showed that it was significantly overexpressed in COPD smokers in comparison to COPD nonsmokers and was only slightly expressed in patients with age-related emphysema.ConclusionαB-crystallin is increased in patients with inflammatory lung diseases. Though unspecific, it could be used in a panel of markers discerning COPD smokers from healthy nonsmokers. As αB-crystallin is a regulator of innate immunity and a therapeutic anti-inflammatory agent, its exact role in COPD pathogenesis and therapy should be explored further.

Strength training elevates HSP27, HSP70 and αB-crystallin levels in musculi vastus lateralis and trapezius

A single bout of high-force exercise has been shown to increase the muscle levels of heat shock proteins (HSPs). Here, changes in the levels of HSPs after 2 and 11 weeks of strength training with either one or three sets per exercise were examined. Fifteen young men (27 ± 6 years, 182 ± 8 cm and 82 ± 13 kg) were randomized to train either one set in lower-body exercises and three sets in upper-body exercises (1L-3UB), or three sets in lower-body exercises and one set in upper-body exercises (3L-1UB). Biopsies from vastus lateralis and trapezius were obtained before, during (2 weeks) and after 11 weeks of strength training (3 bouts per week). The biopsies were analysed for HSP27 (cytosolic and cytoskeletal fractions) and HSP70 and αB-crystallin (cytosolic fraction). No evidence for an effect of training volume (1 vs. 3 sets) on the HSP response was found. For all subjects combined, HSP27 [186 ± 69% (mean ± SD)], HSP70 (146 ± 51%) and αB-crystallin (184 ± 82%) increased in the cytosolic fraction of vastus lateralis after 11 weeks of training. In the trapezius, the only observed increase was for HSP27 in the cytosolic fraction after 2 weeks of training (149 ± 59%). However, the trapezius contained somewhat higher levels of HSP70 and αB-crystallin than vastus lateralis at baseline. The HSP27 levels in the cytoskeletal compartment did not increase significantly in either muscle. In conclusion, strength training resulted-independent of training volume-in elevated levels of HSP27, HSP70 and αB-crystallin in the cytosolic compartment of the vastus lateralis. In the trapezius, only the cytosolic HSP27 levels were increased with training.

Effects of transportation on expression of Hsp90, Hsp70, Hsp27 and αB-crystallin in the pig stomach

Twenty pigs were randomly divided into four groups based on the amount of time spent in transport (zero, one, two or four hours). Pathological examination of all transported pigs showed...

Phosphorylation of Ser45 and Ser59 of αB‐crystallin and p38/extracellular regulated kinase activity determine αB‐crystallin‐mediated protection of rat brain astrocytes from C2‐ceramide‐ and staurosporine‐induced cell death

We previously demonstrated that αB-crystallin and protease-activated receptor (PAR) are involved in protection of astrocytes against C2-ceramide- and staurosporine-induced cell death [Li et al. (2009) J. Neurochem.110, 1433-1444]. Here, we further investigated the mechanism of cytoprotection by αB-crystallin. Our current data revealed that after down-regulation of αB-crystallin by siRNA, cell death caused by C2-ceramide and staurosporine is increased. Furthermore, we investigated the mechanism of cytoprotection of astrocytes by intracellular αB-crystallin. Application of specific inhibitors of p38 and extracellular regulated kinase (ERK) abrogates the protection of astrocytes by over-expression of αB-crystallin. Thus, p38 and ERK contribute to protective processes by αB-crystallin. To reveal the molecular mechanism of αB-crystallin-mediated cytoprotection, we mimicked phosphorylation or unphosphorylation of αB-crystallin. In these experiments, we found that the phosphorylation of αB-crystallin at Ser45 and Ser59 is required for protection. Ser19 phosphorylation of αB-crystallin does not contribute to protection. Moreover, we detected that PAR-2 activation increases the phosphorylation level of αB-crystallin at Ser59, but does not affect the expression level of αB-crystallin. Thus, endogenous αB-crystallin has protective capacity employing a mechanism, which involves regulation of the phosphorylation status of αB-crystallin and p38 and ERK activity. Moreover, we report that PAR-2 activation evokes the phosphorylation of αB-crystallin to increase astrocytes survival.

αB-crystallin, a small heat shock protein, modulates NF-κB activity in a phosphorylation-dependent manner and protects muscle myoblasts from TNF-α induced cytotoxicity

αB-crystallin, a member of the small heat shock protein family, has been implicated in various biological functions including response to heat shock, differentiation and apoptosis, the mechanisms of which have not been well understood. Myoblasts, the precursor cells in muscle regeneration, when subjected to growth factor deprivation differentiate to form myotubes or undergo apoptosis. During differentiation, myoblasts express elevated levels of αB-crystallin as well as TNF-α but the connecting link between these proteins in cell signaling is not clearly understood. We have therefore investigated the role of αB-crystallin in TNF-α induced regulation of NF-κB.We demonstrate that in response to TNF-α treatment, αB-crystallin associates with IKKβ and activate its kinase activity, facilitating the degradation of phosphorylated I-kBα, a prime step in NF-κB activation. Reducing the level of αB-crystallin using the RNAi approach reduces the translocation of p65, further confirming the role of αB-crystallin in NF-κB activation. Our study shows that the ability of αB-crystallin to activate NF-κB depends on its phosphorylation status. The present study shows that αB-crystallin-dependent NF-κB activation protects myoblasts from TNF-α induced cytoxicity by enhancing the expression of the anti-apoptotic protein, Bcl 2. Thus, our study identifies yet another mechanism by which αB-crystallin exerts its anti-apoptotic activity.

Serine 59 Phosphorylation of αB-Crystallin Down-regulates Its Anti-apoptotic Function by Binding and Sequestering Bcl-2 in Breast Cancer Cells

The small heat shock protein (sHSP) αB-crystallin is a new oncoprotein in breast carcinoma that predicts poor clinical outcome in breast cancer. However, although several reports have demonstrated that phosphorylation of sHSPs modify their structural and functional properties, the significance of αB-crystallin phosphorylation in cancer cells has not yet been investigated. In this study, we have characterized the phosphorylation status of αB-crystallin in breast epithelial carcinoma cells line MCF7 submitted to anti-cancer agents like vinblastine. We have showed that the main phosphorylation site of αB-crystallin in response to vinblastine is serine 59 and determined a correlation between this post-translational modification and higher apoptosis level. The overexpression of the serine 59 "pseudophosphorylated" mutant (S59E) induces a significant increase in the apoptosis level of vinblastine-treated MCF7 cells. In contrast, overexpression of wild-type αB-crystallin or "nonphosphorylatable" mutant (S59A) result in a resistance to this microtubule-depolymerizing agent, while inhibition of endogenous levels of αB-crystallin by expression of shRNA lowers it. Analyzing further the molecular mechanism of this phenomenon, we report for the first time that phosphorylated αB-crystallin preferentially interacts with Bcl-2, an anti-apoptotic protein, and this interaction prevents the translocation of Bcl-2 to mitochondria. Hence, this study identifies serine 59 phosphorylation as an important key in the down-regulation of αB-crystallin anti-apoptotic function in breast cancer and suggests new strategies to improve anti-cancer treatments.

Early response of heat shock proteins to functional overload of the soleus and plantaris in rats and mice

Heat shock proteins (HSPs) are important factors in the response of skeletal muscles to chronic increases or decreases in activation and loading. The purpose of this study was to compare species-, time- and muscle-dependent changes in protein expression of Hsp20, Hsp25, αB-crystallin, Hsp72 and Hsp90 in response to functional overload (FO) in rats and mice. We compared protein levels of Hsp20, Hsp25, αB-crystallin, Hsp72 and Hsp90 in soleus and plantaris in baseline conditions and following 0.5, 1, 2, 3 and 7 days (rats) or 3 and 7 days (mice) of FO. Baseline levels of all HSPs were higher in rat soleus than plantaris, whereas only baseline expression of Hsp20 was higher in mouse soleus than plantaris. Levels of Hsp72 and Hsp90 were higher in plantaris and soleus of FO than control mice and rats after 3 and 7 days of FO. Protein levels and phosphorylation of Hsp25 in mouse plantaris and soleus were higher than control levels after 3 and 7 days of FO, except for soleus at 3 days. αB-crystallin levels were higher in plantaris of FO than control mice after 3 and 7 days of FO and in FO than control rats after 7 days of FO. Heat shock protein 20 was the least responsive, increasing only in 7 day FO rat plantaris compared with control rats. Overall, the results demonstrate that levels of both large and small HSPs increase with FO, suggesting a contributory role during the compensatory hypertrophy response.

αB‐crystallin (HspB5) in familial amyloidotic polyneuropathy

The small heat shock protein αB-crystallin (HspB5) is known to be overexpressed in several neurodegenerative disorders. In familial amyloidotic polyneuropathy (FAP), a neurodegenerative disorder characterized by extracellular deposition of mutated transthyretin (TTR), activation of heat shock factor 1 -HSF1- by extracellular TTR deposition has been shown as well as induction of the expression of heat shock proteins, HSP27 and HSP70. Here we investigate the expression of αB-crystallin in FAP. We first detected αB-crystallin in aggregates extracted from tissues of both FAP patients and transgenic mice for the human V30M mutant TTR; however, subsequent studies by confocal fluorescence microscopy did not confirm the association of αB-crystallin with TTR aggregates; thus the presence of αB-crystallin in aggregate extracts might derive from the extraction procedure. Increased levels of αB-crystallin were observed by immunohistochemistry in human FAP skin, as compared to normal skin. Furthermore, skin, stomach and dorsal root ganglia from V30M transgenic mice showed increased expression of αB-crystallin as compared to controls without deposition. A human neuroblastoma cell line incubated with TTR aggregates displayed increased expression of αB-crystallin. Overall, these results show that extracellular TTR deposits induce an intracellular response of αB-crystallin. This small heat shock protein (HSP), which is important for anti-apoptotic and chaperone properties, may have a protective role in FAP.

Increased αB-crystallin in hypothalamic paraventricular nucleus of rats with myocardial infarction

The hypothalamus plays an important role in maintaining a homeostasis of the body against stress response. In particular, the paraventricular nucleus of the hypothalamus is a critical region for disorders related to the autonomic nervous system, such as congestive heart failure and hypertension. αB-crystallin is a family of heat shock proteins that are widely expressed in the brain, including in glial cells, astrocytes, oligodendrocytes, and neurons. Many studies have demonstrated that expression level of αB-crystallin is up-regulated and involved in protecting cells from pathological conditions. In the present study, we examined the expression and potential role of αB-crystallin in the paraventricular nucleus (PVN) regions of rats with myocardial infarction (MI). Our results demonstrate that mRNA encoding αB-crystallin and protein for both native and phosphorylate forms (Ser-59) of αB-crystallin was significantly increased in the PVN during MI.

Oligomers of Mutant Glial Fibrillary Acidic Protein (GFAP) Inhibit the Proteasome System in Alexander Disease Astrocytes, and the Small Heat Shock Protein αB-Crystallin Reverses the Inhibition

The accumulation of the intermediate filament protein, glial fibrillary acidic protein (GFAP), in astrocytes of Alexander disease (AxD) impairs proteasome function in astrocytes. We have explored the molecular mechanism that underlies the proteasome inhibition. We find that both assembled and unassembled wild type (wt) and R239C mutant GFAP protein interacts with the 20 S proteasome complex and that the R239C AxD mutation does not interfere with this interaction. However, the R239C GFAP accumulates to higher levels and forms more protein aggregates than wt protein. These aggregates bind components of the ubiquitin-proteasome system and, thus, may deplete the cytosolic stores of these proteins. We also find that the R239C GFAP has a greater inhibitory effect on proteasome system than wt GFAP. Using a ubiquitin-independent degradation assay in vitro, we observed that the proteasome cannot efficiently degrade unassembled R239C GFAP, and the interaction of R239C GFAP with proteasomes actually inhibits proteasomal protease activity. The small heat shock protein, alphaB-crystallin, which accumulates massively in AxD astrocytes, reverses the inhibitory effects of R239C GFAP on proteasome activity and promotes degradation of the mutant GFAP, apparently by shifting the size of the mutant protein from larger oligomers to smaller oligomers and monomers. These observations suggest that oligomeric forms of GFAP are particularly effective at inhibiting proteasome activity.

Ubiquitin–proteasome-mediated degradation and synthesis of MyoD is modulated by αB-crystallin, a small heat shock protein, during muscle differentiation

αB-crystallin, a small heat shock protein, plays an important role in muscle homeostasis. It gets up-regulated during muscle differentiation and mice lacking αB-crystallin die prematurely with extensive muscle wastage. We have examined the role of αB-crystallin in muscle development using C2C12 myoblasts as a model system. Over-expression of αB-crystallin delays the muscle differentiation program significantly. C2C12 myoblasts over-expressing αB-crystallin (CRYAB-C2C12) display defect in cell-cycle exit upon induction of differentiation. During differentiation, CRYAB-C2C12 cells exhibit sustained level of cyclin D1 and delay in p21 and myogenin expression as compared to C2C12 cells. We find less accumulation of MyoD in CRYAB-C2C12 cells than in C2C12 cells. In vivo protein stability studies reveal faster ubiquitin–proteasome-mediated MyoD degradation in CRYAB-C2C12 cells ( t 1/2 = 1.42 h) than in C2C12 cells ( t 1/2 = 2.37 h). Immuno-precipitation experiments showed that MyoD gets ubiquitinated at earlier time points in CRYAB-C2C12 cells than in C2C12 cells. Our data reveal alterations in the synthesis and degradation of MyoD in CRYAB-C2C12 cells. The level of αB-crystallin as well as its Ser-59 phosphorylated form increases with increasing time of differentiation. Our studies show, inter alia, that αB-crystallin modulates myogenesis by altering MyoD level and provide an interesting insight in its role in myogenesis.

Suppression of Cancer Cell Growth by Promoting Cyclin D1 Degradation

The cyclin D1 proto-oncoprotein is a crucial regulator in cell-cycle progression, and aberrant overexpression of cyclin D1 is linked to tumorigenesis of many different cancer types. By screening ubiquitinated cyclin D1 as a substrate with a deubiquitinase library, we have identified USP2 as a specific deubiquitinase for cyclin D1. USP2 directly interacts with cyclin D1 and promotes its stabilization by antagonizing ubiquitin-dependent degradation. Conversely, USP2 knockdown destabilizes cyclin D1 and induces growth arrest in the human cancer lines where cell growth is dependent on cyclin D1 expression. Of note, cyclin D1 is not universally required for cell-cycle progression. Inactivation of USP2 has either very mild effects on cell growth in normal human fibroblasts or no effect in the cancer cells that do not express cyclin D1. These findings suggest that targeting USP2 is an effective approach to induce growth suppression in the cancer cells addicted to cyclin D1 expression.

Oxidative stress and calpain inhibition induce alpha B-crystallin phosphorylation via p38-MAPK and calcium signalling pathways in H9c2 cells

We investigated the response of αB-crystallin to oxidative stress and calpain inhibition in an attempt to elucidate the signalling pathways mediating its phosphorylation. Given the high expression levels of αB-crystallin in cardiac muscle one can evaluate the significance of its participation in preservation of homeostasis under adverse conditions. H9c2 cardiac myoblasts were used as our experimental model since their response reflects the signal transduction pathways activated by stress conditions in the myocardium. Thus, in H9c2 cells treated with H 2O 2 the mechanism regulating αB-crystallin phosphorylation was found to involve p38-MAPK/MSK1 as well as intracellular free calcium levels. Our immunocytochemical experiments demonstrated phosphorylated αB-crystallin to be co-localized with tubulin, potentially preserving cytoskeletal architecture under these interventions. In H9c2 cells treated with calpain inhibitors (ALLN, ALLM) αB-crystallin exhibited a p38-MAPK- and [Ca 2+] i-dependent phosphorylation pattern since the latter was ablated in the presence of the selective p38-MAPK inhibitor SB203580 and calcium chelator BAPTA-AM. Calpain activity repression ultimately led to apoptosis confirmed by PARP fragmentation and chromatin condensation. However, the apoptotic pathway activated by ALLM and ALLN differed, underlying the diverse transduction mechanisms stimulated. In addition to this, an anti-apoptotic role for phospho-αB-crystallin was verified by confirmation of its interaction with pro-caspase 3, hindering its cleavage and subsequent activation. Collectively, our findings underline αB-crystallin crucial role as a participant of cardiac cells early response to stressful stimuli compromising their survival.

Noninvasive Measurement of Protein Aggregation by Mutant Huntingtin Fragments or α-Synuclein in the Lens

Many diverse human diseases are associated with protein aggregation in ordered fibrillar structures called amyloid. Amyloid formation may mediate aberrant protein interactions that culminate in neurodegeneration in Alzheimer, Huntington, and Parkinson diseases and in prion encephalopathies. Studies of protein aggregation in the brain are hampered by limitations in imaging techniques and often require invasive methods that can only be performed postmortem. Here we describe transgenic mice in which aggregation-prone proteins that cause Huntington and Parkinson disease are expressed in the ocular lens. Expression of a mutant huntingtin fragment or alpha-synuclein in the lens leads to protein aggregation and cataract formation, which can be monitored in real time by noninvasive, highly sensitive optical techniques. Expression of a mutant huntingtin fragment in mice lacking the major lens chaperone, alphaB-crystallin, markedly accelerated the onset and severity of aggregation, demonstrating that the endogenous chaperone activity of alphaB-crystallin suppresses aggregation in vivo. These novel mouse models will facilitate the characterization of protein aggregation in vivo and are being used in efficient and economical screens for chemical and genetic modifiers of disease-relevant protein aggregation.

Genetic, Age and Light Mediated Effects on Crystallin Protein Expression in the Retina

To probe for possible relationships between retinal crystallins and retinal degenerations, protein expression was compared in normal Sprague-Dawley rats, treated or not with intense light, Royal College of Surgeons (RCS) rats and transgenic rats expressing rhodopsin mutations. Rats were reared in dim cyclic light for 21-75 days. Photoreceptor cell DNA levels were determined at various ages to assess the rates of visual cell loss. 1D- and 2D-gel electrophoresis was used to profile retinal protein expression. Crystallins were identified by western analysis and by tandem mass spectrometry. In normal rat retinas, alpha, beta and gamma crystallins were present, although alphaA- and gamma-crystallins exhibited some increase with age. As measured by DNA levels, the rate of genetically induced photoreceptor cell loss was greater in rats with faster degenerating retinas (RCS, S334-ter Line 4, P23H Line 3) than in rats with slower degenerating retinas (S334-ter Line 9, P23H Line 2). In genetic models of retinal degeneration increased levels of immunoreactivity for all crystallins, especially alphaA-insert, correlated with the different rates of photoreceptor loss. In the light induced degeneration model alphaA-insert was unchanged, truncated alphaB-crystallin levels were increased and gamma-crystallins were greatly reduced. In the RCS rat retina 16 different crystallins were identified. Our data suggests that an increase in crystallin expression occurs during various retinal degenerations and that the increases may be related to the severity, type and onset of retinal degeneration.